Pilot Study of Dabrafenib, Trametinib, and Nivolumab Combination for Treating Pediatric BRAF-altered Gliomas

What this Trial Is About

Researchers are studying pediatric gliomas with specific BRAF alterations, such as BRAFV600 mutations or KIAA1549-BRAF fusions, which are usually treated with chemotherapy or MAPK inhibitors like dabrafenib and trametinib. Some of these gliomas may progress or grow back after stopping treatment. This trial explores combining MAPK inhibitors with anti-PD1 therapy nivolumab to potentially improve immune response against tumors in recurrent, refractory low-grade gliomas and newly diagnosed or recurrent high-grade gliomas with BRAF or NF alterations. The study tests two treatment groups Cohort A receives trametinib and nivolumab, while Cohort B receives dabrafenib, trametinib, and nivolumab together. Trametinib is taken orally daily, dabrafenib is taken orally twice daily for Cohort B, and nivolumab is given intravenously every four weeks. Each treatment cycle lasts 28 days, with therapy planned for one year or up to 13 cycles, extendable for high-grade glioma patients if benefits are seen. Participants are followed for up to five years to assess long-term outcomes. Participants undergo evaluations of safety based on side effects during a 28-day dose-limiting toxicity period and effectiveness measures through one year of treatment and five years of follow-up. The study monitors response to therapy, progression-free survival, and overall survival. Ongoing assessments include neurological exams, organ function tests, and clinical status, with treatment tolerability and early efficacy being primary focuses throughout participation.

MAPK Inhibition Combined With Anti-PD1 Therapy for BRAF-altered Pediatric Gliomas