Anaplastic Astrocytoma, Anaplastic Ganglioglioma, Anaplastic Oligodendroglioma, Anaplastic Pleomorphic Xanthoastrocytoma, Angiocentric Glioma, Astrocytoma, Central Neurocytoma, Cerebellar Iponeurocytoma, Chordoid Glioma of Third Ventricle, Desmoplastic Infantile Astrocytoma and Ganglioglioma, Diffuse Astrocytoma, Dysplastic Gangliocytoma of Cerebrellum, Extraventricular Neurocytoma, Gangliocytoma, Ganglioglioma, Giant Cell Astrocytoma, Glioblastoma, Oligodendroglioma, Childhood, Papillary Glioneuronal Tumor, Pilocytic Astrocytoma, Pleomorphic Xanthoastrocytoma, Rosette-forming Glioneurona Tumor
Conditions
Keywords
Malignant glioma, BRAF mutant positive, High grade glioma, Low grade glioma, Dabrafenib, Trametinib, Pediatrics, Brain neoplasma
Brief summary
The purpose of this study was to investigate the activity of dabrafenib in combination with trametinib in children and adolescent patients with BRAF V600 mutation positive low grade glioma (LGG) or relapsed or refractory high grade glioma (HGG)
Detailed description
This study combines two pediatric glioma cohorts (LGG and HGG cohorts) into a multi-center, open-label, Phase II study: * The LGG cohort is a multi-center, randomized, open-label part of this Phase II study conducted in children and adolescent patients with BRAF V600 mutation-positive LGG whose tumor was unresectable and who required first systemic treatment. Participants in the LGG cohort were randomized in a 2:1 ratio to either dabrafenib plus trametinib or carboplatin with vincristine. * The HGG cohort is a multi-center, single-arm, open-label part of this Phase II study conducted in children and adolescent patients with BRAF V600 mutation-positive, refractory or relapsed HGG tumors after having received at least one previous standard therapy. The duration of treatment for participants on dabrafenib plus trametinib in LGG and for all patients in the HGG cohort was continued until the loss of clinical benefit in the opinion of the Investigator, unacceptable toxicity, start of a new anti-neoplastic therapy, discontinuation at the discretion of the investigator or patient/legal guardian, lost to follow-up, death, study termination by the sponsor, or until disease progression. The duration of treatment for patients in the carboplatin with vincristine arm in LGG cohort was continued for the prescribed number of cycles, as tolerated or until unacceptable toxicity, start of a new anti-neoplastic therapy, discontinuation at the discretion of the investigator or patient/legal guardian, lost to follow-up, death, study is terminated by the sponsor or until disease progression. Participants randomized to the carboplatin with vincristine treatment arm were allowed to cross over to receive dabrafenib in combination with trametinib after centrally confirmed RANO-defined disease progression. Crossover was allowed during the treatment period or the post-treatment period. After discontinuation of study treatment, all participants (LGG and HGG cohorts) were followed for safety for at least 30 days after the last dose of study treatment. All participants who discontinued study treatment for reasons other than disease progression, death, loss to follow up, or withdrawal of consent moved into the post-treatment efficacy follow-up phase. Finally, all participants were followed for survival once they discontinued study treatment for at least 2 years after the last patient first study treatment (except if consent was withdrawn, death, or the patient was lost to follow-up or discontinued study)
Interventions
DRUGDabrafenib
Dabrafenib was available as 50 mg and 75 mg hard capsules and as 10 mg dispersible tablets for oral suspension. Dabrafenib was administered orally, twice daily, and was dosed based on age and weight Patients \< 12 years old and ≥ 16 kg were to be administered either the dabrafenib capsules or dabrafenib dispersible tablets for oral suspension (dose: 5.25 mg/kg/day) Patients ≥ 12 years old and ≥ 19 kg were to be administered either the dabrafenib capsules or dabrafenib dispersible tablets for oral suspension (dose: 4.5 mg/kg/day) Patients \< 12 years old and \< 16 kg were to be administered dabrafenib dispersible tablets for oral suspension (dose: 5.25 mg/kg/day) Patients ≥12 years old and \<19 kg were to be administered dabrafenib dispersible tablets for oral suspension (dose: 4.5 mg/kg/day)
DRUGtrametinib
Trametinib was available as 0.5 mg and 2 mg film-coated tablets and as 5.0 mg powder in bottle for oral solution (0.05 mg/ml after reconstitution with 90 ml water).Trametinib was administered orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on age and weight. Patients \<6 years old and \<26 kg were to be administered the trametinib oral solution (dose: 0.032 mg/kg/day) Patients \<6 years old and ≥26 kg were to be administered either the trametinib oral solution or trametinib tablets (dose: 0.032 mg/kg/day) Patients ≥6 years old and ≥10 kg \< 33 kg were to be administered the trametinib oral solution (dose: 0.025 mg/kg/day) Patients ≥6 years old and ≥33 kg were to be administered either the trametinib oral solution or the trametinib tablets (dose: 0.025 mg/kg/day)
DRUGCarboplatin
Carboplatin was supplied locally as commercially available and labelled accordingly to comply with legal requirements of each country. Carboplatin was administered as one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Each maintenance cycle was 6 weeks, and consisted of 4 weeks of chemotherapy with 2 weeks of rest. Induction: 175 mg/m\^2 as weekly intravenous (IV) infusion on weeks 1 to 4, and on weeks 7 to 10, on the same day as vincristine dosing Maintenance: 175 mg/m\^2 as weekly IV infusion over 60 minutes on weeks 1 to 4 of each cycle.
DRUGVincristine
Vincristine was supplied locally as commercially available and labelled accordingly to comply with legal requirements of each country. Vincristine was administered as one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Induction: 1.5 mg/m\^2 as weekly IV bolus infusion (0.05 mg/kg if child is \<12 kg) (maximum dose of 2.0 mg) for 10 weeks. Maintenance: 1.5 mg/m\^2 as weekly IV bolus infusion (0.05 mg/kg if child is \<12 kg) (maximum dose of 2.0 mg) on weeks 1 to 3 of each cycle, on the same day as carboplatin dosing.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Months to 17 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Diagnosis of BRAF V600 mutant High Grade glioma that had relapsed, progressed or failed to respond to frontline therapy * Diagnosis of BRAF V600 mutant Low Grade glioma with progressive disease following surgical excision, or non-surgical candidates with necessity to begin first systemic treatment because of a risk of neurological impairment with progression. * Confirmed measurable disease Key
Exclusion criteria
* Previous treatment with dabrafenib, trametinib, other RAF inhibitor, other MEK or ERK inhibitor * HGG patient: Cancer treatment within the past 3 weeks. LGG patient: Any systemic therapy or radiotherapy prior to enrollment * LGG patients: history of allergic reaction or contraindications to the use of carboplatin or vincristine * Stem cell transplant within the past 3 months * History of heart disease * Pregnant or lactating females
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria | Up to approx. 3.2 years | Percentage of participants in the HGG cohort with a best overall confirmed CR or PR as assessed per RANO criteria by central independent assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. |
| LGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using Response Assessment in Neuro-Oncology (RANO) Criteria | Up to approximately (approx.) 3 years | Percentage of participants in the LGG cohort with a best overall confirmed Complete Response (CR) or Partial Response (PR) as assessed per RANO criteria by central independent assessment. The 95% confidence intervals (CIs) were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria | Up to approx. 3 years and up to approx 4.2 years | Time from first documented response (PR or CR) until disease progression or death as per RANO criteria. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy, were censored at the date of the last adequate tumor evaluation. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. |
| LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria | Up to approx. 3 years and up to approx 4.2 years | Time from first documented response (PR or CR) until disease progression or death as per RANO criteria. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy, were censored at the date of the last adequate tumor evaluation. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. |
| LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria | Up to approx. 3 years and up to approx 4.2 years | Time from the date of randomization to the date of first documented disease progression as per central independent review assessment using RANO criteria or death due to any cause. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation. |
| LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Investigator Assessment Using RANO Criteria | Up to approx. 3 years and up to approx 4.2 years | Time from the date of randomization to the date of first documented disease progression as per investigator assessment using RANO criteria or death due to any cause. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation. |
| LGG Cohort: Kaplan-Meier Estimates of Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria | Up to approx. 4.2 years | Time from randomization to first documented response of CR or PR as per central independent assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients without an event were censored either at the maximum follow-up time (if they experienced disease progression or death), or at their last tumor assessment date. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. |
| LGG Cohort: Kaplan-Meier Estimates of Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria | Up to approx. 4.2 years | Time from randomization to first documented response of CR or PR as per investigator assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients without an event were censored either at the maximum follow-up time (if they experienced disease progression or death), or at their last tumor assessment date. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. |
| LGG Cohort: Clinical Benefit Rate (CBR) by Central Independent Assessment Using RANO Criteria | Up to approx. 4.2 years | Percentage of participants with a best overall response of CR or PR, or stable disease (SD) which lasts for 24 weeks or longer. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. SD: Partient did not qualify for CR, PR, or progressive disease and has stable nonenhancing (T2/FLAIR) lesions on same or lower doses of corticosteroids compared with baseline scan and clinically stable status. |
| LGG Cohort: Clinical Benefit Rate (CBR) by Investigator Assessment Using RANO Criteria | Up to approx. 4.2 years | Percentage of participants with a best overall response of CR or PR, or stable disease (SD) which lasts for 24 weeks or longer. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. SD: Partient did not qualify for CR, PR, or progressive disease and has stable nonenhancing (T2/FLAIR) lesions on same or lower doses of corticosteroids compared with baseline scan and clinically stable status. |
| LGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS) | Up to 4.6 years | Time from first dose to death due to any cause in the LGG cohort. Confidence Intervals were estimated using the Brookmeyer Crowley method. If a patient was not known to have died at the time of analysis cut-off, OS was censored at the date of last contact. |
| LGG Cohort: 2-year OS Estimate | 2 years from first dose | OS was defined as the time from the first dose to death due to any cause in the LGG cohort. The 2-year Kaplan-Meier OS estimate represented the estimated percentage of participants remaining free from OS events for up to 2 years. If a patient was not known to have died at the time of analysis cut-off, OS was censored at the date of last contact |
| HGG Cohort: ORR by Investigator Assessment Using RANO Criteria | Up to approx. 3.2 years and up to approx. 4.8 years | ORR in the HGG cohort defined as the percentage of participants in the HGG cohort with a best overall confirmed CR or PR as assessed per RANO criteria by investigator assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. |
| HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria | Up to approx. 3.2 years and up to approx. 4.8 years | Time from first documented response (PR or CR) until disease progression or death as per central independent assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. |
| HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria | Up to approx. 3.2 years and up to approx. 4.8 years | Time from first documented response (PR or CR) until disease progression or death as per investigator assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. |
| HGG Cohort: Kaplan-Meier Estimates of Progression Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria | Up to approx. 4.8 years | Time from the date of first dose of study treatment to the date of first documented disease progression as per central independent review assessment using RANO criteria or death due to any cause. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation. |
| HGG Cohort: Kaplan-Meier Estimates of Progression Free Survival (PFS) as Per Investigatort Assessment Using RANO Criteria | Up to approx. 4.8 years | Time from the date of first dose of study treatment to the date of first documented disease progression as per investigator assessment using RANO criteria or death due to any cause. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation. |
| HGG Cohort: Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria | Up to approx. 4.8 years | Time from start of treatment to first documented response of CR or PR as per independent assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients without an event were censored either at the maximum follow-up time (if they experienced disease progression or death), or at their last tumor assessment date. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. |
| HGG Cohort: Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria | Up to approx. 4.8 years | Time from start of treatment to first documented response of CR or PR as per investigator assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients without an event were censored either at the maximum follow-up time (if they experienced disease progression or death), or at their last tumor assessment date. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. |
| HGG Cohort: Clinical Benefit Rate (CBR) as Per Central Independent Assessment Using RANO Criteria | Up to approx. 4.8 years | Percentage of participants with a best overall response of CR or PR, or stable disease (SD) which lasts for 24 weeks or longer. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. SD: Partient did not qualify for CR, PR, or progressive disease and has stable nonenhancing (T2/FLAIR) lesions on same or lower doses of corticosteroids compared with baseline scan and clinically stable status. |
| HGG Cohort: Clinical Benefit Rate (CBR) as Per Investigator Assessment Using RANO Criteria | Up to approx. 4.8 years | Percentage of participants with a best overall response of CR or PR, or stable disease (SD) which lasts for 24 weeks or longer. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. SD: Partient did not qualify for CR, PR, or progressive disease and has stable nonenhancing (T2/FLAIR) lesions on same or lower doses of corticosteroids compared with baseline scan and clinically stable status. |
| HGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS) | Up to 5.1 years | Time from first dose to death due to any cause in the LGG cohort. Confidence Intervals were estimated using the Brookmeyer Crowley method. If a patient was not known to have died at the time of analysis cut-off, OS was censored at the date of last contact. |
| AUClast for Trametinib | Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose | Pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast). |
| Cmax for Trametinib | Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose | PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum plasma drug concentration after single dose administration |
| AUCtau for Trametinib | Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose | PK parameters were calculated by standard non-compartmental analysis. AUCtau is the AUC calculated to the end of a dosing interval (tau) at steady-state |
| Tmax for Trametinib | Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose | PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum plasma concentration. Actual recorded sampling times were considered for the calculations. |
| T1/2 for Trametinib | Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose | PK parameters were calculated by standard non-compartmental analysis. T1/2 is the elimination half-life |
| Ctrough for Trametinib | Week 3 Day 1 pre-dose | PK parameters were calculated by standard non-compartmental analysis. Ctrough is the pre-dose plasma concentration |
| AUClast for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose | PK parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast). |
| Cmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose | PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum plasma drug concentration after single dose administration |
| AUCtau for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose | PK parameters were calculated by standard non-compartmental analysis. AUCtau is the AUC calculated to the end of a dosing interval (tau) at steady-state |
| Tmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose | PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum plasma concentration. Actual recorded sampling times were considered for the calculations. |
| T1/2 for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose | PK parameters were calculated by standard non-compartmental analysis. T1/2 is the elimination half-life |
| Ctrough for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Week 3 Day 1 pre-dose | PK parameters were calculated by standard non-compartmental analysis. Ctrough is the pre-dose plasma concentration |
| HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 and Week 5 | Participants who received the dabrafenib dispersible tablets for oral suspension completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on how it tasted before rinsing with water, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes. |
| HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 and Week 5 | Participants who received the trametinib oral solution completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on how it tasted before rinsing with water, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes. |
| HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 and Week 5 | Participants who received the dabrafenib dispersible tablets for oral suspension completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the after-taste of the medication after the medication was swallowed, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes. |
| HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 and Week 5 | Participants who received the trametinib oral solution completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the after-taste of the medication after the medication was swallowed, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes. |
| HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 and Week 5 | Participants who received the dabrafenib dispersible tablets for oral suspension completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the immediate reaction once the medication was placed into their mouth, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes. |
| HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 and Week 5 | Participants who received the trametinib oral solution completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the immediate reaction once the medication was placed into their mouth, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes. |
| HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 and Week 5 | Participants who received the trametinib oral solution completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the after-taste of the medication after rinsing with water, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes. |
| LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Baseline, and Day 1 of Week 5, 8, 16, 24, 32, 49, 48 and 56, and thereafter every 16 weeks until end of treatment (EOT), EOT, and every 16 weeks in the post-treatment efficacy follow-up phase until disease progression (assessed up to 4.6 years) | The PROMIS Parent Proxy Global Health 7+2 was used to evaluate the quality of life of participants. The questionnaire included 7 items measuring the global health of the patient. 4 items used a 5-level Likert scale with 1=poor and 5=excellent; 1 item used a 5-level Likert scale with 1=never and 5=always; and 2 items used a 5-level Likert scale with 1=never and 5=almost always. The total raw global health score, ranging from 7 to 35, was computed by summing item values, with higher scores indicating better overall well-being. Raw scores were then transformed into T-scores, standardized with a mean of 50 and a standard deviation of 10. Higher T-scores reflected better global health status. Participants who discontinued treatment for reasons other than disease progression entered the post-treatment efficacy follow-up phase, where the questionnaire was performed every 16 weeks until disease progression, withdrawal of consent by patient or a parental/legal guardian, or lost to follow-up. |
| LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Baseline, and Day 1 of Week 5, 8, 16, 24, 32, 49, 48 and 56, and thereafter every 16 weeks until end of treatment (EOT), EOT, and every 16 weeks in the post-treatment efficacy follow-up phase until disease progression (assessed up to 4.6 years) | The PROMIS Parent Proxy Global Health 7+2 was used to evaluate the quality of life of participants. The questionnaire included 1 item measuring the pain of the participants. Pain item used a 5-level Likert scale with 1= never and 5= almost always, higher scores indicate worsening pain. Raw scores were then converted into T-scores, standardized with a mean of 50 and a standard deviation of 10. Higher T-scores indicated more severe pain experiences. Participants who discontinued treatment for reasons other than disease progression entered the post-treatment efficacy follow-up phase, where the PROMIS Parent Proxy Global 7+2 Health questionnaire was performed every 16 weeks until disease progression, withdrawal of consent by patient or a parental/legal guardian, or lost to follow-up. |
| LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Baseline, and Day 1 of Week 5, 8, 16, 24, 32, 49, 48 and 56, and thereafter every 16 weeks until end of treatment (EOT), EOT, and every 16 weeks in the post-treatment efficacy follow-up phase until disease progression (assessed up to 4.6 years) | The PROMIS Parent Proxy Global Health 7+2 was used to evaluate the quality of life of participants. The questionnaire included 1 item measuring the fatigue interference of the participants. Fatigue item used a 5-level Likert scale with 1= never and 5= almost always, higher scores indicate worsening fatigue. Raw scores were then converted into T-scores, standardized with a mean of 50 and a standard deviation of 10. Higher T-scores indicated a greater level of reported fatigue. Participants who discontinued treatment for reasons other than disease progression entered the post-treatment efficacy follow-up phase, where the PROMIS Parent Proxy Global 7+2 Health questionnaire was performed every 16 weeks until disease progression, withdrawal of consent by patient or a parental/legal guardian, or lost to follow-up. |
| HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 and Week 5 | Participants who received the dabrafenib dispersible tablets for oral suspension completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the after-taste of the medication after rinsing with water, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes. |
| LGG Cohort: ORR by Investigator Assessment Using RANO Criteria | Up to approx. 3 years and up to approx 4.2 years | Percentage of participants in the LGG cohort with a best overall confirmed CR or PR as assessed per RANO criteria by investigator assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. |
Other
| Measure | Time frame | Description |
|---|---|---|
| LGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria (Longer Follow-up Time) | Up to approx 4.2 years | Percentage of participants with a best overall confirmed CR or PR as assessed per RANO criteria by central independent assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. This analysis was conducted at the end of the trial (after the primary endpoint analysis cut-off date) and includes a longer follow-up time |
| HGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria (Longer Follow-up Time) | Up to approx 4.8 years | Percentage of participants with a best overall confirmed CR or PR as assessed per RANO criteria by central independent assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. This analysis was conducted at the end of the trial (after the primary endpoint analysis cut-off date) and includes a longer follow-up time |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Czechia, Denmark, Finland, France, Germany, Israel, Italy, Japan, Netherlands, Russia, Spain, Sweden, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted in 58 centers across 20 countries
Pre-assignment details
Pediatric patients for both cohorts were screened for eligibility during the 28 days immediately prior to starting study treatment on Day 1. In the LGG cohort, 121 patients were screened of whom 110 patients were randomized in a 2:1 ratio to the dabrafenib and trametinib arm or the carboplatin with vincristine arm. 4 participants randomized to chemotherapy arm were never treated. In the HGG cohort, 46 patients were screened of whom 41 patients entered the HGG cohort
Participants by arm
| Arm | Count |
|---|---|
| LGG Cohort: Dabrafenib and Trametinib Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight) | 73 |
| LGG Cohort: Carboplatin and Vincristine Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression. | 37 |
| HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight) | 41 |
| Total | 151 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Crossover Treatment Period | Progressive disease | 0 | 1 | 0 |
| Post-treatment Efficacy Follow-up | Death | 0 | 0 | 3 |
| Post-treatment Efficacy Follow-up | New therapy for study indication | 0 | 1 | 0 |
| Post-treatment Efficacy Follow-up | Physician Decision | 1 | 2 | 0 |
| Post-treatment Efficacy Follow-up | Progressive disease | 4 | 3 | 0 |
| Post-treatment Efficacy Follow-up | Subject/guardian decision | 2 | 2 | 0 |
| Post-treatment Survival Follow-up | Death | 0 | 0 | 7 |
| Post-treatment Survival Follow-up | Lack of Efficacy | 1 | 0 | 0 |
| Treatment Period | Adverse Event | 3 | 8 | 1 |
| Treatment Period | Death | 0 | 0 | 2 |
| Treatment Period | New therapy for study indication | 1 | 0 | 0 |
| Treatment Period | Physician Decision | 5 | 1 | 2 |
| Treatment Period | Progressive disease | 4 | 10 | 19 |
| Treatment Period | Protocol deviation | 0 | 1 | 0 |
| Treatment Period | Subject/guardian decision | 4 | 3 | 0 |
Baseline characteristics
| Characteristic | LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: Carboplatin and Vincristine | HGG Cohort: Dabrafenib and Trametinib | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 73 Participants | 37 Participants | 41 Participants | 151 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 3 Participants | 11 Participants | 19 Participants |
| Race/Ethnicity, Customized Black Or African American | 2 Participants | 3 Participants | 1 Participants | 6 Participants |
| Race/Ethnicity, Customized Not Reported | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Unknown | 6 Participants | 4 Participants | 3 Participants | 13 Participants |
| Race/Ethnicity, Customized White | 55 Participants | 25 Participants | 25 Participants | 105 Participants |
| Sex: Female, Male Female | 44 Participants | 22 Participants | 23 Participants | 89 Participants |
| Sex: Female, Male Male | 29 Participants | 15 Participants | 18 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 41 | 11 / 13 | 0 / 73 | 0 / 11 | 0 / 33 | 0 / 16 | 1 / 12 | 0 / 0 |
| other Total, other adverse events | 41 / 41 | 0 / 0 | 73 / 73 | 0 / 0 | 33 / 33 | 0 / 0 | 11 / 12 | 0 / 0 |
| serious Total, serious adverse events | 28 / 41 | 0 / 0 | 34 / 73 | 0 / 0 | 14 / 33 | 0 / 0 | 4 / 12 | 0 / 0 |
Outcome results
Primary
HGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria
Percentage of participants in the HGG cohort with a best overall confirmed CR or PR as assessed per RANO criteria by central independent assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.
Time frame: Up to approx. 3.2 years
Population: All participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | HGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria | 56.1 Percentage of participants |
Primary
LGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using Response Assessment in Neuro-Oncology (RANO) Criteria
Percentage of participants in the LGG cohort with a best overall confirmed Complete Response (CR) or Partial Response (PR) as assessed per RANO criteria by central independent assessment. The 95% confidence intervals (CIs) were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.
Time frame: Up to approximately (approx.) 3 years
Population: All participants on the LGG cohort to whom study treatment had been assigned by randomization regardless of whether or not treatment was administered. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using Response Assessment in Neuro-Oncology (RANO) Criteria | 46.6 Percentage of participants |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using Response Assessment in Neuro-Oncology (RANO) Criteria | 10.8 Percentage of participants |
p-value: <0.00195% CI: [2.3, 22.4]Chi-squared
Secondary
AUClast for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)
PK parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast).
Time frame: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose
Population: Participants who received at least one dose of dabrafenib with an evaluable AUClast PK parameter
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | AUClast for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Dabrafenib | 4330 hr * ng/ml | Geometric Coefficient of Variation 44.7 |
| LGG Cohort: Dabrafenib and Trametinib | AUClast for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Carboxy-dabrafenib | 73400 hr * ng/ml | Geometric Coefficient of Variation 31.5 |
| LGG Cohort: Dabrafenib and Trametinib | AUClast for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Desmethyl-dabrafenib | 3520 hr * ng/ml | Geometric Coefficient of Variation 60.2 |
| LGG Cohort: Dabrafenib and Trametinib | AUClast for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Hydroxy-dabrafenib | 2810 hr * ng/ml | Geometric Coefficient of Variation 36.5 |
| LGG Cohort: Carboplatin and Vincristine | AUClast for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Hydroxy-dabrafenib | 2980 hr * ng/ml | Geometric Coefficient of Variation 50.1 |
| LGG Cohort: Carboplatin and Vincristine | AUClast for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Dabrafenib | 4870 hr * ng/ml | Geometric Coefficient of Variation 60.3 |
| LGG Cohort: Carboplatin and Vincristine | AUClast for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Desmethyl-dabrafenib | 3870 hr * ng/ml | Geometric Coefficient of Variation 68.2 |
| LGG Cohort: Carboplatin and Vincristine | AUClast for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Carboxy-dabrafenib | 64200 hr * ng/ml | Geometric Coefficient of Variation 46.9 |
Secondary
AUClast for Trametinib
Pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast).
Time frame: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose
Population: Participants who received at least one dose of trametinib with an evaluable AUClast PK parameter
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | AUClast for Trametinib | 282 hour (hr) * nanogram (ng)/mililiter (mL) | Geometric Coefficient of Variation 53.7 |
| LGG Cohort: Carboplatin and Vincristine | AUClast for Trametinib | 328 hour (hr) * nanogram (ng)/mililiter (mL) | Geometric Coefficient of Variation 33.4 |
Secondary
AUCtau for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)
PK parameters were calculated by standard non-compartmental analysis. AUCtau is the AUC calculated to the end of a dosing interval (tau) at steady-state
Time frame: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose
Population: Participants who received at least one dose of dabrafenib with an evaluable AUCtau PK parameter
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | AUCtau for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Dabrafenib | 4300 hr * ng/ml | Geometric Coefficient of Variation 44.7 |
| LGG Cohort: Dabrafenib and Trametinib | AUCtau for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Carboxy-dabrafenib | 71200 hr * ng/ml | Geometric Coefficient of Variation 34 |
| LGG Cohort: Dabrafenib and Trametinib | AUCtau for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Desmethyl-dabrafenib | 3360 hr * ng/ml | Geometric Coefficient of Variation 57.7 |
| LGG Cohort: Dabrafenib and Trametinib | AUCtau for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Hydroxy-dabrafenib | 2840 hr * ng/ml | Geometric Coefficient of Variation 35.7 |
| LGG Cohort: Carboplatin and Vincristine | AUCtau for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Hydroxy-dabrafenib | 2960 hr * ng/ml | Geometric Coefficient of Variation 47.4 |
| LGG Cohort: Carboplatin and Vincristine | AUCtau for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Dabrafenib | 4910 hr * ng/ml | Geometric Coefficient of Variation 54 |
| LGG Cohort: Carboplatin and Vincristine | AUCtau for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Desmethyl-dabrafenib | 3660 hr * ng/ml | Geometric Coefficient of Variation 66.9 |
| LGG Cohort: Carboplatin and Vincristine | AUCtau for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Carboxy-dabrafenib | 60700 hr * ng/ml | Geometric Coefficient of Variation 45.7 |
Secondary
AUCtau for Trametinib
PK parameters were calculated by standard non-compartmental analysis. AUCtau is the AUC calculated to the end of a dosing interval (tau) at steady-state
Time frame: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose
Population: Participants who received at least one dose of trametinib with an evaluable AUCtau PK parameter
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | AUCtau for Trametinib | 307 hr * ng/mL | Geometric Coefficient of Variation 22.8 |
| LGG Cohort: Carboplatin and Vincristine | AUCtau for Trametinib | 339 hr * ng/mL | Geometric Coefficient of Variation 22.2 |
Secondary
Cmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)
PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum plasma drug concentration after single dose administration
Time frame: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose
Population: Participants who received at least one dose of dabrafenib with an evaluable Cmax PK parameter
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | Cmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Dabrafenib | 1520 ng/ml | Geometric Coefficient of Variation 65.9 |
| LGG Cohort: Dabrafenib and Trametinib | Cmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Carboxy-dabrafenib | 9050 ng/ml | Geometric Coefficient of Variation 31.4 |
| LGG Cohort: Dabrafenib and Trametinib | Cmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Desmethyl-dabrafenib | 388 ng/ml | Geometric Coefficient of Variation 67.2 |
| LGG Cohort: Dabrafenib and Trametinib | Cmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Hydroxy-dabrafenib | 801 ng/ml | Geometric Coefficient of Variation 58.8 |
| LGG Cohort: Carboplatin and Vincristine | Cmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Hydroxy-dabrafenib | 687 ng/ml | Geometric Coefficient of Variation 82.6 |
| LGG Cohort: Carboplatin and Vincristine | Cmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Dabrafenib | 1330 ng/ml | Geometric Coefficient of Variation 93.5 |
| LGG Cohort: Carboplatin and Vincristine | Cmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Desmethyl-dabrafenib | 377 ng/ml | Geometric Coefficient of Variation 67.2 |
| LGG Cohort: Carboplatin and Vincristine | Cmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Carboxy-dabrafenib | 7210 ng/ml | Geometric Coefficient of Variation 51.6 |
Secondary
Cmax for Trametinib
PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum plasma drug concentration after single dose administration
Time frame: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose
Population: Participants who received at least one dose of trametinib with an evaluable Cmax PK parameter
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | Cmax for Trametinib | 21.3 ng/mL | Geometric Coefficient of Variation 36.3 |
| LGG Cohort: Carboplatin and Vincristine | Cmax for Trametinib | 22.7 ng/mL | Geometric Coefficient of Variation 41.1 |
Secondary
Ctrough for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)
PK parameters were calculated by standard non-compartmental analysis. Ctrough is the pre-dose plasma concentration
Time frame: Week 3 Day 1 pre-dose
Population: Participants who received at least one dose of dabrafenib with an evaluable Ctrough PK parameter
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | Ctrough for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Dabrafenib | 38.0 ng/ml | Geometric Coefficient of Variation 162 |
| LGG Cohort: Dabrafenib and Trametinib | Ctrough for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Carboxy-dabrafenib | 3980 ng/ml | Geometric Coefficient of Variation 46.1 |
| LGG Cohort: Dabrafenib and Trametinib | Ctrough for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Desmethyl-dabrafenib | 275 ng/ml | Geometric Coefficient of Variation 116.5 |
| LGG Cohort: Dabrafenib and Trametinib | Ctrough for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Hydroxy-dabrafenib | 41.8 ng/ml | Geometric Coefficient of Variation 123.8 |
| LGG Cohort: Carboplatin and Vincristine | Ctrough for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Hydroxy-dabrafenib | 44.3 ng/ml | Geometric Coefficient of Variation 99.7 |
| LGG Cohort: Carboplatin and Vincristine | Ctrough for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Dabrafenib | 46.0 ng/ml | Geometric Coefficient of Variation 125.1 |
| LGG Cohort: Carboplatin and Vincristine | Ctrough for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Desmethyl-dabrafenib | 310 ng/ml | Geometric Coefficient of Variation 70.1 |
| LGG Cohort: Carboplatin and Vincristine | Ctrough for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Carboxy-dabrafenib | 3190 ng/ml | Geometric Coefficient of Variation 54.4 |
Secondary
Ctrough for Trametinib
PK parameters were calculated by standard non-compartmental analysis. Ctrough is the pre-dose plasma concentration
Time frame: Week 3 Day 1 pre-dose
Population: Participants who received at least one dose of trametinib with an evaluable Ctrough PK parameter
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | Ctrough for Trametinib | 8.73 ng/ml | Geometric Coefficient of Variation 72.7 |
| LGG Cohort: Carboplatin and Vincristine | Ctrough for Trametinib | 9.82 ng/ml | Geometric Coefficient of Variation 30.1 |
Secondary
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed
Participants who received the dabrafenib dispersible tablets for oral suspension completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the after-taste of the medication after the medication was swallowed, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes.
Time frame: Week 1 and Week 5
Population: Participants who received at least one dose of dabrafenib as dispersible tablet for oral suspension and completed the palatability questionnaire for dabrafenib at week 1 or 5.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 | Very good, good, and neither good nor bad | 4 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 | Bad | 1 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 | Very bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 | Unable to answer question | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 | Missing | 3 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 5 | Very good, good, and neither good nor bad | 5 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 5 | Bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 5 | Very bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 5 | Unable to answer question | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 5 | Missing | 3 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 5 | Very bad | 0 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 | Very good, good, and neither good nor bad | 13 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 5 | Very good, good, and neither good nor bad | 16 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 | Bad | 6 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 5 | Missing | 11 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 | Very bad | 0 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 5 | Bad | 2 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 | Unable to answer question | 3 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 5 | Unable to answer question | 3 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 | Missing | 10 Participants |
Secondary
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth
Participants who received the dabrafenib dispersible tablets for oral suspension completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the immediate reaction once the medication was placed into their mouth, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes.
Time frame: Week 1 and Week 5
Population: Participants who received at least one dose of dabrafenib as dispersible tablet for oral suspension and completed the palatability questionnaire for dabrafenib at week 1 or 5.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 | Very good, good, and neither good nor bad | 4 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 | Bad | 1 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 | Very bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 | Unable to answer question | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 | Missing | 3 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 5 | Very good, good, and neither good nor bad | 5 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 5 | Bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 5 | Very bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 5 | Unable to answer question | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 5 | Missing | 3 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 5 | Very bad | 0 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 | Very good, good, and neither good nor bad | 13 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 5 | Very good, good, and neither good nor bad | 18 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 | Bad | 5 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 5 | Missing | 11 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 | Very bad | 1 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 5 | Bad | 1 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 | Unable to answer question | 3 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 5 | Unable to answer question | 2 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 | Missing | 10 Participants |
Secondary
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water
Participants who received the dabrafenib dispersible tablets for oral suspension completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the after-taste of the medication after rinsing with water, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes.
Time frame: Week 1 and Week 5
Population: Participants who received at least one dose of dabrafenib as dispersible tablet for oral suspension and completed the palatability questionnaire for dabrafenib at week 1 or 5.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 | Very good, good, and neither good nor bad | 4 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 | Bad | 2 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 | Very bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 | Unable to answer question | 1 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 | Missing | 1 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water | Week 5 | Very good, good, and neither good nor bad | 6 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water | Week 5 | Bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water | Week 5 | Very bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water | Week 5 | Unable to answer question | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water | Week 5 | Missing | 2 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water | Week 5 | Very bad | 1 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 | Very good, good, and neither good nor bad | 15 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water | Week 5 | Very good, good, and neither good nor bad | 17 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 | Bad | 5 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water | Week 5 | Missing | 8 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 | Very bad | 0 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water | Week 5 | Bad | 2 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 | Unable to answer question | 7 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water | Week 5 | Unable to answer question | 4 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 | Missing | 5 Participants |
Secondary
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth
Participants who received the dabrafenib dispersible tablets for oral suspension completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on how it tasted before rinsing with water, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes.
Time frame: Week 1 and Week 5
Population: Participants who received at least one dose of dabrafenib as dispersible tablet for oral suspension and completed the palatability questionnaire for dabrafenib at week 1 or 5.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 | Very good, good, and neither good nor bad | 5 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 | Bad | 2 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 | Very bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 | Unable to answer question | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 | Missing | 1 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 5 | Very good, good, and neither good nor bad | 6 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 5 | Bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 5 | Very bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 5 | Unable to answer question | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 5 | Missing | 2 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 5 | Very bad | 1 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 | Very good, good, and neither good nor bad | 18 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 5 | Very good, good, and neither good nor bad | 20 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 | Bad | 4 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 5 | Missing | 8 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 | Very bad | 0 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 5 | Bad | 1 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 | Unable to answer question | 5 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 5 | Unable to answer question | 2 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 | Missing | 5 Participants |
Secondary
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed
Participants who received the trametinib oral solution completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the after-taste of the medication after the medication was swallowed, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes.
Time frame: Week 1 and Week 5
Population: Participants who received at least one dose of trametinib oral solution and completed the palatability questionnaire for trametinib at week 1 or 5.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 | Very good, good, and neither good nor bad | 3 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 | Bad | 3 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 | Very bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 | Unable to answer question | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 | Missing | 2 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 5 | Very good, good, and neither good nor bad | 5 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 5 | Bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 5 | Very bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 5 | Unable to answer question | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 5 | Missing | 3 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 5 | Very bad | 1 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 | Very good, good, and neither good nor bad | 15 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 5 | Very good, good, and neither good nor bad | 16 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 | Bad | 5 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 5 | Missing | 13 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 | Very bad | 2 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 5 | Bad | 3 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 | Unable to answer question | 2 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 5 | Unable to answer question | 2 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed | Week 1 | Missing | 11 Participants |
Secondary
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth
Participants who received the trametinib oral solution completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the immediate reaction once the medication was placed into their mouth, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes.
Time frame: Week 1 and Week 5
Population: Participants who received at least one dose of trametinib oral solution and completed the palatability questionnaire for trametinib at week 1 or 5.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 | Very good, good, and neither good nor bad | 3 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 | Bad | 3 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 | Very Bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 | Unable to answer question | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 | Missing | 2 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 5 | Very good, good, and neither good nor bad | 5 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 5 | Bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 5 | Very Bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 5 | Unable to answer question | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 5 | Missing | 3 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 5 | Very Bad | 2 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 | Very good, good, and neither good nor bad | 15 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 5 | Very good, good, and neither good nor bad | 15 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 | Bad | 4 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 5 | Missing | 13 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 | Very Bad | 3 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 5 | Bad | 4 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 | Unable to answer question | 2 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 5 | Unable to answer question | 1 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth | Week 1 | Missing | 11 Participants |
Secondary
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water
Participants who received the trametinib oral solution completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the after-taste of the medication after rinsing with water, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes.
Time frame: Week 1 and Week 5
Population: Participants who received at least one dose of trametinib oral solution and completed the palatability questionnaire for trametinib at week 1 or 5.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 | Very Bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water | Week 5 | Very good, good, and neither good nor bad | 4 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 | Bad | 2 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water | Week 5 | Bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 | Unable to answer question | 2 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water | Week 5 | Very Bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 | Very good, good, and neither good nor bad | 2 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 | Missing | 2 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water | Week 5 | Missing | 3 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water | Week 5 | Unable to answer question | 1 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water | Week 5 | Missing | 14 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 | Very good, good, and neither good nor bad | 15 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 | Bad | 3 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 | Very Bad | 2 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 | Unable to answer question | 6 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water | Week 1 | Missing | 9 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water | Week 5 | Very good, good, and neither good nor bad | 14 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water | Week 5 | Bad | 2 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water | Week 5 | Very Bad | 2 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water | Week 5 | Unable to answer question | 3 Participants |
Secondary
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth
Participants who received the trametinib oral solution completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on how it tasted before rinsing with water, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes.
Time frame: Week 1 and Week 5
Population: Participants who received at least one dose of trametinib oral solution and completed the palatability questionnaire for trametinib at week 1 or 5.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 | Very good, good, and neither good nor bad | 2 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 | Bad | 3 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 | Very bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 | Unable to answer question | 1 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 | Missing | 2 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 5 | Very good, good, and neither good nor bad | 5 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 5 | Bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 5 | Very bad | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 5 | Unable to answer question | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 5 | Missing | 3 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 5 | Very bad | 2 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 | Very good, good, and neither good nor bad | 15 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 5 | Very good, good, and neither good nor bad | 12 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 | Bad | 5 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 5 | Missing | 14 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 | Very bad | 2 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 5 | Bad | 6 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 | Unable to answer question | 4 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 5 | Unable to answer question | 1 Participants |
| LGG Cohort: Carboplatin and Vincristine | HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth | Week 1 | Missing | 9 Participants |
Secondary
HGG Cohort: Clinical Benefit Rate (CBR) as Per Central Independent Assessment Using RANO Criteria
Percentage of participants with a best overall response of CR or PR, or stable disease (SD) which lasts for 24 weeks or longer. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. SD: Partient did not qualify for CR, PR, or progressive disease and has stable nonenhancing (T2/FLAIR) lesions on same or lower doses of corticosteroids compared with baseline scan and clinically stable status.
Time frame: Up to approx. 4.8 years
Population: All participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | HGG Cohort: Clinical Benefit Rate (CBR) as Per Central Independent Assessment Using RANO Criteria | 65.9 Percentage of participants |
Secondary
HGG Cohort: Clinical Benefit Rate (CBR) as Per Investigator Assessment Using RANO Criteria
Percentage of participants with a best overall response of CR or PR, or stable disease (SD) which lasts for 24 weeks or longer. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. SD: Partient did not qualify for CR, PR, or progressive disease and has stable nonenhancing (T2/FLAIR) lesions on same or lower doses of corticosteroids compared with baseline scan and clinically stable status.
Time frame: Up to approx. 4.8 years
Population: All participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | HGG Cohort: Clinical Benefit Rate (CBR) as Per Investigator Assessment Using RANO Criteria | 75.6 Percentage of participants |
Secondary
HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria
Time from first documented response (PR or CR) until disease progression or death as per central independent assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.
Time frame: Up to approx. 3.2 years and up to approx. 4.8 years
Population: Participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment with a confirmed CR or PR as per central independent assessment using RANO criteria
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria | Up to approx. 3.2 years | 22.2 Months |
| LGG Cohort: Dabrafenib and Trametinib | HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria | Up to approx. 4.8 years | 27.4 Months |
Secondary
HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria
Time from first documented response (PR or CR) until disease progression or death as per investigator assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.
Time frame: Up to approx. 3.2 years and up to approx. 4.8 years
Population: Participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment with a confirmed CR or PR as per investigator assessment using RANO criteria
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria | Up to approx. 3.2 years | 26.6 Months |
| LGG Cohort: Dabrafenib and Trametinib | HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria | Up to approx. 4.8 years | 32.7 Months |
Secondary
HGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS)
Time from first dose to death due to any cause in the LGG cohort. Confidence Intervals were estimated using the Brookmeyer Crowley method. If a patient was not known to have died at the time of analysis cut-off, OS was censored at the date of last contact.
Time frame: Up to 5.1 years
Population: All participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | HGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS) | NA Months |
Secondary
HGG Cohort: Kaplan-Meier Estimates of Progression Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria
Time from the date of first dose of study treatment to the date of first documented disease progression as per central independent review assessment using RANO criteria or death due to any cause. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation.
Time frame: Up to approx. 4.8 years
Population: All participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | HGG Cohort: Kaplan-Meier Estimates of Progression Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria | 9.0 Months |
Secondary
HGG Cohort: Kaplan-Meier Estimates of Progression Free Survival (PFS) as Per Investigatort Assessment Using RANO Criteria
Time from the date of first dose of study treatment to the date of first documented disease progression as per investigator assessment using RANO criteria or death due to any cause. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation.
Time frame: Up to approx. 4.8 years
Population: All participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | HGG Cohort: Kaplan-Meier Estimates of Progression Free Survival (PFS) as Per Investigatort Assessment Using RANO Criteria | 24.0 Months |
Secondary
HGG Cohort: ORR by Investigator Assessment Using RANO Criteria
ORR in the HGG cohort defined as the percentage of participants in the HGG cohort with a best overall confirmed CR or PR as assessed per RANO criteria by investigator assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.
Time frame: Up to approx. 3.2 years and up to approx. 4.8 years
Population: All participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | HGG Cohort: ORR by Investigator Assessment Using RANO Criteria | Up to approx. 3.2 years | 58.5 Percentage of participants |
| LGG Cohort: Dabrafenib and Trametinib | HGG Cohort: ORR by Investigator Assessment Using RANO Criteria | Up to approx. 4.8 years | 61.0 Percentage of participants |
Secondary
HGG Cohort: Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria
Time from start of treatment to first documented response of CR or PR as per independent assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients without an event were censored either at the maximum follow-up time (if they experienced disease progression or death), or at their last tumor assessment date. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.
Time frame: Up to approx. 4.8 years
Population: All participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | HGG Cohort: Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria | 8.5 Months |
Secondary
HGG Cohort: Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria
Time from start of treatment to first documented response of CR or PR as per investigator assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients without an event were censored either at the maximum follow-up time (if they experienced disease progression or death), or at their last tumor assessment date. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.
Time frame: Up to approx. 4.8 years
Population: All participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | HGG Cohort: Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria | 3.4 Months |
Secondary
LGG Cohort: 2-year OS Estimate
OS was defined as the time from the first dose to death due to any cause in the LGG cohort. The 2-year Kaplan-Meier OS estimate represented the estimated percentage of participants remaining free from OS events for up to 2 years. If a patient was not known to have died at the time of analysis cut-off, OS was censored at the date of last contact
Time frame: 2 years from first dose
Population: All participants on the LGG cohort to whom study treatment had been assigned by randomization regardless of whether or not treatment was administered. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: 2-year OS Estimate | 100.0 Percentage of participants |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: 2-year OS Estimate | 96.9 Percentage of participants |
Secondary
LGG Cohort: Clinical Benefit Rate (CBR) by Central Independent Assessment Using RANO Criteria
Percentage of participants with a best overall response of CR or PR, or stable disease (SD) which lasts for 24 weeks or longer. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. SD: Partient did not qualify for CR, PR, or progressive disease and has stable nonenhancing (T2/FLAIR) lesions on same or lower doses of corticosteroids compared with baseline scan and clinically stable status.
Time frame: Up to approx. 4.2 years
Population: All participants on the LGG cohort to whom study treatment had been assigned by randomization regardless of whether or not treatment was administered. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: Clinical Benefit Rate (CBR) by Central Independent Assessment Using RANO Criteria | 86.3 Percentage of participants |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: Clinical Benefit Rate (CBR) by Central Independent Assessment Using RANO Criteria | 43.2 Percentage of participants |
Secondary
LGG Cohort: Clinical Benefit Rate (CBR) by Investigator Assessment Using RANO Criteria
Percentage of participants with a best overall response of CR or PR, or stable disease (SD) which lasts for 24 weeks or longer. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. SD: Partient did not qualify for CR, PR, or progressive disease and has stable nonenhancing (T2/FLAIR) lesions on same or lower doses of corticosteroids compared with baseline scan and clinically stable status.
Time frame: Up to approx. 4.2 years
Population: All participants on the LGG cohort to whom study treatment had been assigned by randomization regardless of whether or not treatment was administered. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: Clinical Benefit Rate (CBR) by Investigator Assessment Using RANO Criteria | 91.8 Percentage of participants |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: Clinical Benefit Rate (CBR) by Investigator Assessment Using RANO Criteria | 56.8 Percentage of participants |
Secondary
LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria
Time from first documented response (PR or CR) until disease progression or death as per RANO criteria. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy, were censored at the date of the last adequate tumor evaluation. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.
Time frame: Up to approx. 3 years and up to approx 4.2 years
Population: Participants on the LGG cohort to whom study treatment had been assigned by randomization regardless of whether or not treatment was administered with a confirmed CR or PR as per central independent review assessment using RANO criteria. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria | Up to approx. 3 years | 20.3 Months |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria | Up to approx 4.2 years | 30.0 Months |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria | Up to approx. 3 years | NA Months |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria | Up to approx 4.2 years | 19.4 Months |
Secondary
LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria
Time from first documented response (PR or CR) until disease progression or death as per RANO criteria. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy, were censored at the date of the last adequate tumor evaluation. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.
Time frame: Up to approx. 3 years and up to approx 4.2 years
Population: Participants on the LGG cohort to whom study treatment had been assigned by randomization regardless of whether or not treatment was administered with a confirmed CR or PR as per investigator review assessment using RANO criteria. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria | Up to approx. 3 years | NA Months |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria | Up to approx 4.2 years | 44.4 Months |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria | Up to approx. 3 years | NA Months |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria | Up to approx 4.2 years | 22.5 Months |
Secondary
LGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS)
Time from first dose to death due to any cause in the LGG cohort. Confidence Intervals were estimated using the Brookmeyer Crowley method. If a patient was not known to have died at the time of analysis cut-off, OS was censored at the date of last contact.
Time frame: Up to 4.6 years
Population: All participants on the LGG cohort to whom study treatment had been assigned by randomization regardless of whether or not treatment was administered. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS) | NA Months |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS) | NA Months |
Secondary
LGG Cohort: Kaplan-Meier Estimates of Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria
Time from randomization to first documented response of CR or PR as per central independent assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients without an event were censored either at the maximum follow-up time (if they experienced disease progression or death), or at their last tumor assessment date. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.
Time frame: Up to approx. 4.2 years
Population: Participants on the LGG cohort to whom study treatment had been assigned by randomization regardless of whether or not treatment was administered. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: Kaplan-Meier Estimates of Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria | 11.0 Months |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: Kaplan-Meier Estimates of Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria | NA Months |
Secondary
LGG Cohort: Kaplan-Meier Estimates of Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria
Time from randomization to first documented response of CR or PR as per investigator assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients without an event were censored either at the maximum follow-up time (if they experienced disease progression or death), or at their last tumor assessment date. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.
Time frame: Up to approx. 4.2 years
Population: Participants on the LGG cohort to whom study treatment had been assigned by randomization regardless of whether or not treatment was administered. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: Kaplan-Meier Estimates of Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria | 7.4 Months |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: Kaplan-Meier Estimates of Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria | NA Months |
Secondary
LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria
Time from the date of randomization to the date of first documented disease progression as per central independent review assessment using RANO criteria or death due to any cause. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation.
Time frame: Up to approx. 3 years and up to approx 4.2 years
Population: Participants on the LGG cohort to whom study treatment had been assigned by randomization regardless of whether or not treatment was administered. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria | Up to approx 4.2 years | 24.9 Months |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria | Up to approx. 3 years | 20.1 Months |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria | Up to approx. 3 years | 7.4 Months |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria | Up to approx 4.2 years | 7.2 Months |
Comparison: Up to approx. 3 yearsp-value: <0.00195% CI: [0.17, 0.55]Log Rank
Secondary
LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Investigator Assessment Using RANO Criteria
Time from the date of randomization to the date of first documented disease progression as per investigator assessment using RANO criteria or death due to any cause. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation.
Time frame: Up to approx. 3 years and up to approx 4.2 years
Population: Participants on the LGG cohort to whom study treatment had been assigned by randomization regardless of whether or not treatment was administered. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Investigator Assessment Using RANO Criteria | Up to approx. 3 years | NA Months |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Investigator Assessment Using RANO Criteria | Up to approx 4.2 years | 46.0 Months |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Investigator Assessment Using RANO Criteria | Up to approx. 3 years | NA Months |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Investigator Assessment Using RANO Criteria | Up to approx 4.2 years | 30.8 Months |
Secondary
LGG Cohort: ORR by Investigator Assessment Using RANO Criteria
Percentage of participants in the LGG cohort with a best overall confirmed CR or PR as assessed per RANO criteria by investigator assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.
Time frame: Up to approx. 3 years and up to approx 4.2 years
Population: All participants on the LGG cohort to whom study treatment had been assigned by randomization regardless of whether or not treatment was administered. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: ORR by Investigator Assessment Using RANO Criteria | Up to approx. 3 years | 54.8 Percentage of participants |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: ORR by Investigator Assessment Using RANO Criteria | Up to approx. 4.2 years | 58.9 Percentage of participants |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: ORR by Investigator Assessment Using RANO Criteria | Up to approx. 3 years | 13.5 Percentage of participants |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: ORR by Investigator Assessment Using RANO Criteria | Up to approx. 4.2 years | 18.9 Percentage of participants |
Secondary
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score
The PROMIS Parent Proxy Global Health 7+2 was used to evaluate the quality of life of participants. The questionnaire included 1 item measuring the fatigue interference of the participants. Fatigue item used a 5-level Likert scale with 1= never and 5= almost always, higher scores indicate worsening fatigue. Raw scores were then converted into T-scores, standardized with a mean of 50 and a standard deviation of 10. Higher T-scores indicated a greater level of reported fatigue. Participants who discontinued treatment for reasons other than disease progression entered the post-treatment efficacy follow-up phase, where the PROMIS Parent Proxy Global 7+2 Health questionnaire was performed every 16 weeks until disease progression, withdrawal of consent by patient or a parental/legal guardian, or lost to follow-up.
Time frame: Baseline, and Day 1 of Week 5, 8, 16, 24, 32, 49, 48 and 56, and thereafter every 16 weeks until end of treatment (EOT), EOT, and every 16 weeks in the post-treatment efficacy follow-up phase until disease progression (assessed up to 4.6 years)
Population: All participants on the LGG cohort to whom study treatment had been assigned by randomization regardless of whether or not treatment was administered and contributed to this analysis. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure. Number analyzed indicated number of participants with available data for this outcome measure at the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Baseline | 53.30 Score on a Scale | Standard Deviation 6.731 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 32 Day 1 | 52.49 Score on a Scale | Standard Deviation 7.219 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 40 Day 1 | 52.27 Score on a Scale | Standard Deviation 7.45 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 48 Day 1 | 51.65 Score on a Scale | Standard Deviation 7.362 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 56 Day 1 | 50.51 Score on a Scale | Standard Deviation 7.15 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 72 Day 1 | 49.93 Score on a Scale | Standard Deviation 6.91 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 88 Day 1 | 50.52 Score on a Scale | Standard Deviation 7.358 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 104 Day 1 | 51.11 Score on a Scale | Standard Deviation 6.899 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 120 Day 1 | 50.40 Score on a Scale | Standard Deviation 7.317 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 136 Day 1 | 50.97 Score on a Scale | Standard Deviation 8.667 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 152 Day 1 | 47.71 Score on a Scale | Standard Deviation 8.037 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 168 Day 1 | 48.21 Score on a Scale | Standard Deviation 8.188 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | EOT | 52.35 Score on a Scale | Standard Deviation 7.565 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Post Treatment Follow-Up 1 | 48.94 Score on a Scale | — |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Post Treatment Follow-Up 2 | 62.62 Score on a Scale | — |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Post Treatment Follow-Up 3 | 48.94 Score on a Scale | — |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Post Treatment Follow-Up 4 | 56.07 Score on a Scale | — |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Post Treatment Follow-Up 5 | 62.62 Score on a Scale | — |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 5 Day 1 | 53.96 Score on a Scale | Standard Deviation 7.588 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 8 Day 1 | 52.68 Score on a Scale | Standard Deviation 6.967 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 16 Day 1 | 51.22 Score on a Scale | Standard Deviation 6.983 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 24 Day 1 | 51.04 Score on a Scale | Standard Deviation 8.005 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Baseline | 54.37 Score on a Scale | Standard Deviation 7.981 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | EOT | 56.88 Score on a Scale | Standard Deviation 5.246 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 5 Day 1 | 56.88 Score on a Scale | Standard Deviation 6.43 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Post Treatment Follow-Up 4 | 48.94 Score on a Scale | Standard Deviation 0 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 8 Day 1 | 58.10 Score on a Scale | Standard Deviation 4.823 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Post Treatment Follow-Up 1 | 52.36 Score on a Scale | Standard Deviation 6.84 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 16 Day 1 | 57.81 Score on a Scale | Standard Deviation 6.193 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Post Treatment Follow-Up 8 | 48.94 Score on a Scale | — |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 24 Day 1 | 55.02 Score on a Scale | Standard Deviation 7.248 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Post Treatment Follow-Up 2 | 62.62 Score on a Scale | — |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 32 Day 1 | 57.66 Score on a Scale | Standard Deviation 5.899 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Post Treatment Follow-Up 5 | 48.94 Score on a Scale | — |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 40 Day 1 | 58.49 Score on a Scale | Standard Deviation 7.072 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Post Treatment Follow-Up 3 | 48.94 Score on a Scale | — |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 48 Day 1 | 53.48 Score on a Scale | Standard Deviation 8.004 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Post Treatment Follow-Up 6 | 55.78 Score on a Scale | Standard Deviation 9.673 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score | Week 56 Day 1 | 57.63 Score on a Scale | Standard Deviation 7.254 |
Secondary
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score
The PROMIS Parent Proxy Global Health 7+2 was used to evaluate the quality of life of participants. The questionnaire included 7 items measuring the global health of the patient. 4 items used a 5-level Likert scale with 1=poor and 5=excellent; 1 item used a 5-level Likert scale with 1=never and 5=always; and 2 items used a 5-level Likert scale with 1=never and 5=almost always. The total raw global health score, ranging from 7 to 35, was computed by summing item values, with higher scores indicating better overall well-being. Raw scores were then transformed into T-scores, standardized with a mean of 50 and a standard deviation of 10. Higher T-scores reflected better global health status. Participants who discontinued treatment for reasons other than disease progression entered the post-treatment efficacy follow-up phase, where the questionnaire was performed every 16 weeks until disease progression, withdrawal of consent by patient or a parental/legal guardian, or lost to follow-up.
Time frame: Baseline, and Day 1 of Week 5, 8, 16, 24, 32, 49, 48 and 56, and thereafter every 16 weeks until end of treatment (EOT), EOT, and every 16 weeks in the post-treatment efficacy follow-up phase until disease progression (assessed up to 4.6 years)
Population: All participants on the LGG cohort to whom study treatment had been assigned by randomization (regardless of whether or not treatment was administered) and contributed to this analysis. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure.~Number analyzed indicated number of participants with available data for this outcome measure at the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Post Treatment Follow-Up 2 | 27.70 Score on a Scale | — |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 8 Day 1 | 43.83 Score on a Scale | Standard Deviation 9.461 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 24 Day 1 | 45.27 Score on a Scale | Standard Deviation 9.168 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 32 Day 1 | 45.46 Score on a Scale | Standard Deviation 8.887 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 40 Day 1 | 45.37 Score on a Scale | Standard Deviation 9.687 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 48 Day 1 | 44.83 Score on a Scale | Standard Deviation 9.421 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 56 Day 1 | 44.54 Score on a Scale | Standard Deviation 8.876 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 72 Day 1 | 44.21 Score on a Scale | Standard Deviation 8.967 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 88 Day 1 | 44.91 Score on a Scale | Standard Deviation 8.847 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 104 Day 1 | 45.60 Score on a Scale | Standard Deviation 8.231 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 120 Day 1 | 44.41 Score on a Scale | Standard Deviation 7.317 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 136 Day 1 | 44.45 Score on a Scale | Standard Deviation 8.074 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 152 Day 1 | 47.88 Score on a Scale | Standard Deviation 10.534 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 168 Day 1 | 46.48 Score on a Scale | Standard Deviation 9.888 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | EOT | 44.98 Score on a Scale | Standard Deviation 10.274 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Post Treatment Follow-Up 1 | 45.40 Score on a Scale | — |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Post Treatment Follow-Up 3 | 43.60 Score on a Scale | — |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Post Treatment Follow-Up 4 | 31.20 Score on a Scale | — |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Post Treatment Follow-Up 5 | 29.40 Score on a Scale | — |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Baseline | 42.67 Score on a Scale | Standard Deviation 10.068 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 5 Day 1 | 42.14 Score on a Scale | Standard Deviation 9.439 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 16 Day 1 | 44.68 Score on a Scale | Standard Deviation 9.159 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 56 Day 1 | 38.66 Score on a Scale | Standard Deviation 8.851 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | EOT | 39.69 Score on a Scale | Standard Deviation 10.536 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Baseline | 42.89 Score on a Scale | Standard Deviation 10.502 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Post Treatment Follow-Up 8 | 37.90 Score on a Scale | — |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 5 Day 1 | 39.06 Score on a Scale | Standard Deviation 10.109 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 8 Day 1 | 38.36 Score on a Scale | Standard Deviation 7.759 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Post Treatment Follow-Up 1 | 45.53 Score on a Scale | Standard Deviation 6.288 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 16 Day 1 | 41.11 Score on a Scale | Standard Deviation 10.798 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Post Treatment Follow-Up 2 | 39.70 Score on a Scale | — |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 24 Day 1 | 36.57 Score on a Scale | Standard Deviation 6.241 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Post Treatment Follow-Up 5 | 37.90 Score on a Scale | — |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 32 Day 1 | 40.96 Score on a Scale | Standard Deviation 7.159 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Post Treatment Follow-Up 3 | 34.60 Score on a Scale | — |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 40 Day 1 | 38.84 Score on a Scale | Standard Deviation 4.96 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Post Treatment Follow-Up 6 | 36.45 Score on a Scale | Standard Deviation 7.425 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Week 48 Day 1 | 41.56 Score on a Scale | Standard Deviation 6.953 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score | Post Treatment Follow-Up 4 | 43.60 Score on a Scale | Standard Deviation 8.061 |
Secondary
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score
The PROMIS Parent Proxy Global Health 7+2 was used to evaluate the quality of life of participants. The questionnaire included 1 item measuring the pain of the participants. Pain item used a 5-level Likert scale with 1= never and 5= almost always, higher scores indicate worsening pain. Raw scores were then converted into T-scores, standardized with a mean of 50 and a standard deviation of 10. Higher T-scores indicated more severe pain experiences. Participants who discontinued treatment for reasons other than disease progression entered the post-treatment efficacy follow-up phase, where the PROMIS Parent Proxy Global 7+2 Health questionnaire was performed every 16 weeks until disease progression, withdrawal of consent by patient or a parental/legal guardian, or lost to follow-up.
Time frame: Baseline, and Day 1 of Week 5, 8, 16, 24, 32, 49, 48 and 56, and thereafter every 16 weeks until end of treatment (EOT), EOT, and every 16 weeks in the post-treatment efficacy follow-up phase until disease progression (assessed up to 4.6 years)
Population: All participants on the LGG cohort to whom study treatment had been assigned by randomization (regardless of whether or not treatment was administered) and contributed to this analysis. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure.~Number analyzed indicated number of participants with available data for this outcome measure at the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Baseline | 52.14 Score on a Scale | Standard Deviation 7.658 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 32 Day 1 | 48.77 Score on a Scale | Standard Deviation 6.647 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 40 Day 1 | 49.87 Score on a Scale | Standard Deviation 6.389 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 48 Day 1 | 49.89 Score on a Scale | Standard Deviation 6.581 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 56 Day 1 | 48.14 Score on a Scale | Standard Deviation 6.496 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 72 Day 1 | 49.46 Score on a Scale | Standard Deviation 6.498 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 88 Day 1 | 47.82 Score on a Scale | Standard Deviation 6.083 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 104 Day 1 | 48.74 Score on a Scale | Standard Deviation 6.605 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 120 Day 1 | 48.56 Score on a Scale | Standard Deviation 7.583 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 136 Day 1 | 46.16 Score on a Scale | Standard Deviation 5.305 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 152 Day 1 | 47.42 Score on a Scale | Standard Deviation 6.765 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 168 Day 1 | 48.61 Score on a Scale | Standard Deviation 6.298 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | EOT | 51.46 Score on a Scale | Standard Deviation 6.83 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Post Treatment Follow-Up 1 | 53.05 Score on a Scale | — |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Post Treatment Follow-Up 2 | 58.51 Score on a Scale | — |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Post Treatment Follow-Up 3 | 53.05 Score on a Scale | — |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Post Treatment Follow-Up 4 | 58.51 Score on a Scale | — |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Post Treatment Follow-Up 5 | 58.51 Score on a Scale | — |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 5 Day 1 | 50.11 Score on a Scale | Standard Deviation 7.275 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 8 Day 1 | 49.93 Score on a Scale | Standard Deviation 7.727 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 16 Day 1 | 49.72 Score on a Scale | Standard Deviation 7.3 |
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 24 Day 1 | 50.65 Score on a Scale | Standard Deviation 7.45 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Baseline | 52.64 Score on a Scale | Standard Deviation 7.054 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | EOT | 52.87 Score on a Scale | Standard Deviation 6.113 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 5 Day 1 | 50.97 Score on a Scale | Standard Deviation 6.263 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Post Treatment Follow-Up 4 | 43.25 Score on a Scale | Standard Deviation 0 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 8 Day 1 | 51.00 Score on a Scale | Standard Deviation 6.037 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Post Treatment Follow-Up 1 | 50.60 Score on a Scale | Standard Deviation 4.9 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 16 Day 1 | 51.75 Score on a Scale | Standard Deviation 6.33 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Post Treatment Follow-Up 8 | 43.25 Score on a Scale | — |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 24 Day 1 | 51.81 Score on a Scale | Standard Deviation 7.937 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Post Treatment Follow-Up 2 | 43.25 Score on a Scale | — |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 32 Day 1 | 49.59 Score on a Scale | Standard Deviation 6.387 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Post Treatment Follow-Up 5 | 43.25 Score on a Scale | — |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 40 Day 1 | 52.52 Score on a Scale | Standard Deviation 7.402 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Post Treatment Follow-Up 3 | 43.25 Score on a Scale | — |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 48 Day 1 | 51.20 Score on a Scale | Standard Deviation 5.903 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Post Treatment Follow-Up 6 | 50.88 Score on a Scale | Standard Deviation 10.79 |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score | Week 56 Day 1 | 53.99 Score on a Scale | Standard Deviation 5.466 |
Secondary
T1/2 for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)
PK parameters were calculated by standard non-compartmental analysis. T1/2 is the elimination half-life
Time frame: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose
Population: Participants who received at least one dose of dabrafenib with an evaluable T1/2 PK parameter
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | T1/2 for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Dabrafenib | 2.48 hr | Geometric Coefficient of Variation 36.6 |
| LGG Cohort: Dabrafenib and Trametinib | T1/2 for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Carboxy-dabrafenib | 7.12 hr | Geometric Coefficient of Variation 32.3 |
| LGG Cohort: Dabrafenib and Trametinib | T1/2 for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Desmethyl-dabrafenib | 7.06 hr | Geometric Coefficient of Variation 392.5 |
| LGG Cohort: Dabrafenib and Trametinib | T1/2 for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Hydroxy-dabrafenib | 2.66 hr | Geometric Coefficient of Variation 47.8 |
| LGG Cohort: Carboplatin and Vincristine | T1/2 for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Hydroxy-dabrafenib | 3.52 hr | Geometric Coefficient of Variation 71.7 |
| LGG Cohort: Carboplatin and Vincristine | T1/2 for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Dabrafenib | 3.09 hr | Geometric Coefficient of Variation 36.4 |
| LGG Cohort: Carboplatin and Vincristine | T1/2 for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Desmethyl-dabrafenib | 16.1 hr | — |
| LGG Cohort: Carboplatin and Vincristine | T1/2 for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Carboxy-dabrafenib | 6.59 hr | Geometric Coefficient of Variation 43.9 |
Secondary
T1/2 for Trametinib
PK parameters were calculated by standard non-compartmental analysis. T1/2 is the elimination half-life
Time frame: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose
Population: Participants who received at least one dose of trametinib with an evaluable T1/2 PK parameter
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | T1/2 for Trametinib | 26.7 hour | Geometric Coefficient of Variation 62.6 |
| LGG Cohort: Carboplatin and Vincristine | T1/2 for Trametinib | 25.7 hour | Geometric Coefficient of Variation 37.9 |
Secondary
Tmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)
PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum plasma concentration. Actual recorded sampling times were considered for the calculations.
Time frame: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose
Population: Participants who received at least one dose of dabrafenib with an evaluable Tmax PK parameter
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | Tmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Dabrafenib | 1.47 hr | Geometric Coefficient of Variation 54.2 |
| LGG Cohort: Dabrafenib and Trametinib | Tmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Carboxy-dabrafenib | 3.37 hr | Geometric Coefficient of Variation 35.4 |
| LGG Cohort: Dabrafenib and Trametinib | Tmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Desmethyl-dabrafenib | 2.21 hr | Geometric Coefficient of Variation 76.7 |
| LGG Cohort: Dabrafenib and Trametinib | Tmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Hydroxy-dabrafenib | 1.97 hr | Geometric Coefficient of Variation 45.9 |
| LGG Cohort: Carboplatin and Vincristine | Tmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Hydroxy-dabrafenib | 1.68 hr | Geometric Coefficient of Variation 57.8 |
| LGG Cohort: Carboplatin and Vincristine | Tmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Dabrafenib | 1.47 hr | Geometric Coefficient of Variation 52.9 |
| LGG Cohort: Carboplatin and Vincristine | Tmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Desmethyl-dabrafenib | 2.29 hr | Geometric Coefficient of Variation 82 |
| LGG Cohort: Carboplatin and Vincristine | Tmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) | Carboxy-dabrafenib | 3.66 hr | Geometric Coefficient of Variation 51.4 |
Secondary
Tmax for Trametinib
PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum plasma concentration. Actual recorded sampling times were considered for the calculations.
Time frame: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose
Population: Participants who received at least one dose of trametinib with an evaluable Tmax PK parameter
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | Tmax for Trametinib | 1.67 hour | Geometric Coefficient of Variation 58.1 |
| LGG Cohort: Carboplatin and Vincristine | Tmax for Trametinib | 1.53 hour | Geometric Coefficient of Variation 54.6 |
Post Hoc
All-collected Deaths
On-treatment deaths were collected from 1st dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment (efficacy/survival) follow-up deaths were collected from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG). For participants in the LGG cohort who crossed over to dabrafenib and trametinib, on-treatment deaths were collected from 1st dose to 30 days after last dose of crossover treatment, up to 4.2 years. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Time frame: On-treatment: Up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment: Up to 4.6 years (LGG) and 5.1 years (HGG).Crossover arm: on-treatment: up to 4.2 years
Population: Safety set including all participants who received at least one dose of study treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | All-collected Deaths | Crossover post-treatment efficacy/survival follow-up deaths | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | All-collected Deaths | All deaths | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | All-collected Deaths | On- treatment deaths | 0 Participants |
| LGG Cohort: Dabrafenib and Trametinib | All-collected Deaths | Post-treatment efficacy/survival follow-up deaths | 0 Participants |
| LGG Cohort: Carboplatin and Vincristine | All-collected Deaths | Crossover post-treatment efficacy/survival follow-up deaths | 0 Participants |
| LGG Cohort: Carboplatin and Vincristine | All-collected Deaths | Post-treatment efficacy/survival follow-up deaths | 0 Participants |
| LGG Cohort: Carboplatin and Vincristine | All-collected Deaths | On- treatment deaths | 0 Participants |
| LGG Cohort: Carboplatin and Vincristine | All-collected Deaths | All deaths | 1 Participants |
| LGG Cohort: Carboplatin and Vincristine | All-collected Deaths | Crossover on-treatment deaths | 1 Participants |
| HGG Cohort: Dabrafenib and Trametinib | All-collected Deaths | All deaths | 17 Participants |
| HGG Cohort: Dabrafenib and Trametinib | All-collected Deaths | On- treatment deaths | 6 Participants |
| HGG Cohort: Dabrafenib and Trametinib | All-collected Deaths | Post-treatment efficacy/survival follow-up deaths | 11 Participants |
| HGG Cohort: Dabrafenib and Trametinib | All-collected Deaths | Crossover post-treatment efficacy/survival follow-up deaths | 0 Participants |
Other Pre-specified
HGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria (Longer Follow-up Time)
Percentage of participants with a best overall confirmed CR or PR as assessed per RANO criteria by central independent assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. This analysis was conducted at the end of the trial (after the primary endpoint analysis cut-off date) and includes a longer follow-up time
Time frame: Up to approx 4.8 years
Population: All participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | HGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria (Longer Follow-up Time) | 56.1 Percentage of participants |
Other Pre-specified
LGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria (Longer Follow-up Time)
Percentage of participants with a best overall confirmed CR or PR as assessed per RANO criteria by central independent assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. This analysis was conducted at the end of the trial (after the primary endpoint analysis cut-off date) and includes a longer follow-up time
Time frame: Up to approx 4.2 years
Population: All participants on the LGG cohort to whom study treatment had been assigned by randomization regardless of whether or not treatment was administered. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LGG Cohort: Dabrafenib and Trametinib | LGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria (Longer Follow-up Time) | 54.8 Percentage of participants |
| LGG Cohort: Carboplatin and Vincristine | LGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria (Longer Follow-up Time) | 16.2 Percentage of participants |