Pediatric Long-Term Follow-up and Rollover Study

Study Overview
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Brief Summary
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A roll-over study to assess long-term effect in pediatric patients treated with dabrafenib and/or trametinib.

Official Title
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An Open Label, Multi-center Roll-over Study to Assess Long-term Effect in Pediatric Patients Treated With Tafinlar (Dabrafenib) and/or Mekinist (Trametinib)

Conditions
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Diffuse Astrocytoma, Anaplastic Astrocytoma, Astrocytoma, Oligodendroglioma, Childhood, Anaplastic Oligodendroglioma, Glioblastoma, Pilocytic Astrocytoma, Giant Cell Astrocytoma, Pleomorphic Xanthoastrocytoma, Anaplastic Pleomorphic Xanthoastrocytoma, Angiocentric Glioma, Chordoid Glioma of Third Ventricle, Gangliocytoma, Ganglioglioma, Anaplastic Ganglioglioma, Dysplastic Gangliocytoma of Cerebrellum, Desmoplastic Infantile Astrocytoma and Ganglioglioma, Papillary Glioneuronal Tumor, Rosette-forming Glioneurona Tumor, Central Neurocytoma, Extraventricular Neurocytoma, Cerebellar Liponeurocytoma, Neurofibromatosis Type 1

Intervention / Treatment
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* Drug: dabrafenib
* Drug: trametinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dabrafenib and/or trametinib<br>Patients in this study may receive one of the following treatments received in the parent study which are: Patients who received monotherapy of either of dabrafenib or trametinib Patients who received combination of dabrafenib and trametinib Patients who discontinued treatment on parent study are still offered to participate in long-term follow-up | Drug: dabrafenib<br>* dabrafenib oral, twice daily<br>* Other names: DRB436;Drug: trametinib<br>* trametinib oral, once daily<br>* Other names: TMT212;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse Events and Serious Adverse Events (SAEs) | To assess the long-term safety of treatment with dabrafenib, trametinib or the combination. | Baseline up to approximately 7 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with height (measured by cm or in) changes over time | Developmental monitoring: Serial measurements of height will be collected throughout the study | Baseline up to approximately 7 years | 
| Percentage of participants with weight (measured by kg or lb) changes over time | Developmental monitoring: Serial measurements of weight will be collected throughout the study | Baseline up to approximately 7 years | 
| Percentage of participants with skeletal maturation (measured by bone age on x-ray or MRI) changes over time | Developmental monitoring: Serial measurements of skeletal maturation will be collected throughout the study | Baseline up to approximately 7 years | 
| Percentage of participants with sexual maturation (measured by tanner staging criteria) changes over time | Developmental monitoring: Serial measurements of sexual maturation will be collected throughout the study | Baseline up to approximately 7 years | 
| Percentage of participants with cardiac function (measured by ECG) changes over time | Developmental monitoring: Serial measurements of cardiac function will be collected throughout the study | Baseline up to approximately 7 years | 
| Clinical Benefit (measured by CT/MRI) | 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). | Baseline up to approximately 7 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NF-1, plexiform neurofibromas, v600-mutation, neuroblastoma, Trametinib, pediatrics, Langerhans Cell Histiocytosis, low grade glioma, high grade glioma, dabrafenib