Phase 2 Study of Lowering or Stopping Dabrafenib and Trametinib in Patients Aged 1 to 25 With BRAF V600 Mutant Low-Grade Gliomas

What this Trial Is About

This trial evaluates different ways of reducing the use of the drugs dabrafenib and trametinib in patients with low-grade gliomas that have a BRAF V600 gene mutation. These drugs belong to a class called kinase inhibitors and work by blocking abnormal proteins that cause tumor cells to multiply. The study aims to find the best dosing method for patients who have already been treated with these drugs for 12 to 24 months, comparing stopping treatment completely versus gradually lowering the dose over six months. Participants receive dabrafenib taken twice daily and trametinib once daily in 28-day cycles for at least 12 cycles and up to 24 cycles if the disease does not progress or cause unacceptable side effects. After this period, participants are randomly assigned to either stop the drugs completely or continue with a reduced dose for an additional six cycles. Throughout the study, participants may undergo imaging tests like MRI and ECHO, as well as blood sample collection, and optionally lumbar puncture to collect cerebrospinal fluid. During the study, participants are monitored for tumor response and side effects, including profiling of cell-free DNA and assessing drug toxicity. Researchers measure rebound rates and clinical progression up to 34 months. After treatment ends, participants have a follow-up visit at 30 days and are monitored for up to five years to assess long-term outcomes. The study also explores advanced imaging and machine learning models to evaluate tumor response and investigates microbiome changes and skin toxicity differences across participants.

Dabrafenib and Trametinib for BRAF V600 Mutant Low-Grade Gliomas