Anaplastic Astrocytoma, Anaplastic Ganglioglioma, Anaplastic Oligodendroglioma, Anaplastic Pleomorphic Xanthoastrocytoma, Angiocentric Glioma, Astrocytoma, Central Neurocytoma, Cerebellar Liponeurocytoma, Chordoid Glioma of Third Ventricle, Desmoplastic Infantile Astrocytoma and Ganglioglioma, Diffuse Astrocytoma, Dysplastic Gangliocytoma of Cerebrellum, Extraventricular Neurocytoma, Gangliocytoma, Ganglioglioma, Giant Cell Astrocytoma, Glioblastoma, Neurofibromatosis Type 1, Oligodendroglioma, Childhood, Papillary Glioneuronal Tumor, Pilocytic Astrocytoma, Pleomorphic Xanthoastrocytoma, Rosette-forming Glioneuronal Tumor
Conditions
Keywords
v600-mutation, neuroblastoma, Trametinib, pediatrics, Langerhans Cell Histiocytosis, low grade glioma, plexiform neurofibromas, high grade glioma, dabrafenib, NF-1
Brief summary
A roll-over study to assess long-term effect in pediatric patients treated with dabrafenib and/or trametinib.
Interventions
DRUGdabrafenib
dabrafenib oral, twice daily
DRUGtrametinib
trametinib oral, once daily
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: All Subjects: * Written informed consent, according to local guidelines, signed by the subjects and/or by the parents or legal guardian prior to any study related screening procedures are performed. * Participation in a Novartis sponsored study such as CTMT212X2101, CDRB436G2201, CDRB436A2102, regardless of current age. * Parent study (or cohort of parent study) is planned to be closed. * Subject has demonstrated compliance, as assessed by the investigator, within the parent study protocol requirement(s). * Willingness and ability to comply with scheduled visits, treatment plans and any other study procedures. For Subjects Entering the Treatment Period: * Subject is currently receiving treatment with dabrafenib/trametinib monotherapy or combination within a Novartis Sponsored Drug Development study. Note that subjects who were on the chemotherapy arm of the CDRB436G2201 study are eligible for treatment period of this study only after crossing over into the experimental treatment arm of the CDRB436G2201 study * In the opinion of the investigator is likely to benefit from continued treatment. Key
Exclusion criteria
All Subjects: \- Subject has participated in a combination trial where dabrafenib and/or trametinib was dispensed in combination with another study medication. For Subjects Entering the Treatment Period: * Subject has permanently discontinued from study treatment in the parent protocol due to any reason. * Treatment with dabrafenib and/or trametinib for the subject's indication is approved for marketing and the appropriate dosage form is commercially available and reimbursed in the local country * Subject currently has unresolved drug related severe toxicities for which dabrafenib and/or trametinib dosing has been interrupted in the parent study. If the subject should meet criteria to resume treatment on the parent protocol then they may be eligible for treatment in this study. Other protocol-defined inclusion/exclusion may apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Adverse Events and Serious Adverse Events (SAEs) | Baseline up to approximately 7 years | To assess the long-term safety of treatment with dabrafenib, trametinib or the combination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants with height (measured by cm or in) changes over time | Baseline up to approximately 7 years | Developmental monitoring: Serial measurements of height will be collected throughout the study |
| Percentage of participants with weight (measured by kg or lb) changes over time | Baseline up to approximately 7 years | Developmental monitoring: Serial measurements of weight will be collected throughout the study |
| Percentage of participants with skeletal maturation (measured by bone age on x-ray or MRI) changes over time | Baseline up to approximately 7 years | Developmental monitoring: Serial measurements of skeletal maturation will be collected throughout the study |
| Percentage of participants with sexual maturation (measured by tanner staging criteria) changes over time | Baseline up to approximately 7 years | Developmental monitoring: Serial measurements of sexual maturation will be collected throughout the study |
| Percentage of participants with cardiac function (measured by ECG) changes over time | Baseline up to approximately 7 years | Developmental monitoring: Serial measurements of cardiac function will be collected throughout the study |
| Clinical Benefit (measured by CT/MRI) | Baseline up to approximately 7 years | Disease specific clinical benefit, as determined by investigator using institutional standard of care. Investigator will measure tumor response based on the Response Assessment used for the subject in the parent protocol (Response Assessment in Neuro-Oncology (RANO) criteria for solid tumors, RECIST, NF1 Volumetric, Neuroblastoma, or LCH criteria). |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Czechia, Denmark, Finland, France, Germany, Israel, Italy, Japan, Netherlands, Russia, Spain, Sweden, United Kingdom, United States
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed