braintumor glioma
Conditions
Interventions
Childeren with HGG will be treated with dabrafenib (capsules or oral solution),
twice daily and trametinib (tablets or oral solution), once daily based onbased
on weight, age and appropirate dose le
Sponsors
Novartis
Eligibility
Age
2 Years to 17 Years
Inclusion criteria
Inclusion criteria: - Male or female >= 1 and =50%. - Adequate bone marrow function in the absence of growth factor support. - Adequate renal function, liver function, and cardiac function. - If receiving glucocorticoids, patient must be on a stable or weaning dose for at least 7 days prior to first dose of study treatment.
Exclusion criteria
Exclusion criteria: - Malignancy OTHER than BRAF V600 mutant HGG and LGG. - Previous treatment with dabrafenib or another RAF inhibitor, trametinib or another MEK inhibitor, or an ERK inhibitor. - HGG: Cancer therapy or investigational drugs within 3 weeks preceding the first dose of study treatment. - LGG: Any systemic anticancer therapy or investigational drugs prior to enrollment. - HGG: Radiotherapy to CNS glioma lesions within 3 months prior to first dose of study treatment, unless there is clear evidence of radiologic progression outside of the field of radiation. - LGG: Radiotherapy to CNS glioma lesions at any point prior to enrollment. - History of malignancy with confirmed activating RAS mutation or with BRAF fusion such as BRF-KIAA1549. - Current use of a prohibited medication or herbal preparation or requires any of these medications during the study. See Section 6.4 for details of the protocol. - Unresolved toxicity greater than NCI CTCAE v 4.03 grade 2 from previous anti-cancer therapy, - History of allergic reactions attributed to compounds of similar chemical or biologic composition to dabrafenib, trametinib and their excipients. LGG also history of allergic reactions or contraindications to the use of carboplatin or vincristine. - Autologous or allogeneic stem cell transplant within 3 months prior to the first dose of study treatment - History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study - Uncontrolled medical conditions, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol. - Presence of active GI disease or other condition that will interfere significantly with the absorption of drugs.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective for HGG cohort is: to evaluate the anti-tumor activity of dabrafenib in combination with trametinib as measured by overall response rate (ORR) to the combination therapy by investigator assessment using the RANO criteria. The primary objective for LGG cohort is: Compare the anti-tumor activity of dabrafenib in combination with trametinib versus carboplatin with vincristine, as measured by overall response rate (ORR) by central independent assessment using the RANO criteria. | — |
Secondary
| Measure | Time frame |
|---|---|
| For HGG: 1. Evaluate ORR by central independent review 2. Evaluate duration of response (DOR) by investigator and central independent review 3. Evaluate time to response (TTR) by investigator and central independent review 4. Evaluate progression free survival (PFS) by investigator and central independent review 5. Evaluate overall survival (OS) 6. Evaluate the safety profile of dabrafenib in combination with trametinib in the study population 7. To characterize the pharmacokinetics of dabrafenib, its metabolites and trametinib in the study population For LGG: 1. ORR by central independent review assessment per RANO criteria 2. DOR, calculated as the time from the date of the first documented confirmed response (CR or PR) to the first documented progression or death due to any cause, as assessed separately by investigator and central independent reviewer per RANO criteria. 3. PFS, defined as time from first dose of study treatment to progression or death due to any cause, as assessed separately by central independent reviewer and investigator per RANO criteria 4. TTR, calculated as the time from the start date of study treatment to first documented confirmed response CR or PR (which must be confirmed subsequently) as assessed separately by investigator and independent central reviewer per RANO criteria 5. OS, defined as the time from first dose of study treatment to death due to any cause 6. Incidence of adverse events and serious adverse events, changes in laboratory results, vital signs, ECG and ECHO. 7. To characterize the pharmacokinetics of dabrafenib, its metabolites and trametinib in the study population For both cohorts LGG and HGG: Plasma concentration-time profiles of dabrafenib, its metabolites and trametinib and PK parameters | — |
Countries
Netherlands
Outcome results
None listed