026-20 | Dabrafenib Combined With Trametinib After Radiation Therapy in Treating Patients With Newly-Diagnosed High-Grade Glioma

Overview

“A Phase 2 Study of Dabrafenib (NSC# 763760) with Trametinib (NSC# 763093) after Local Irradiation in Newly-Diagnosed BRAFV600-Mutant High-Grade Glioma (HGG) (IND# 145355)”

Pediatric high-grade gliomas (HGGs), including glioblastoma (GBMs) and anaplastic astrocytoma (AAs), represent approximately 15% of all newly-diagnosed central nervous system (CNS) tumors in children.1 Unfortunately, despite improvement in neurosurgical techniques, radiation therapy (RT) delivery, and trials of various chemotherapy agents, the survival of children with HGG has not significantly changed in the past several decades. No effective curative salvage therapy is available at the time of tumor progression. New treatment strategies for pediatric HGGs are urgently required. In recent years, there have been considerable advances in defining subsets of pediatric HGG by genotyping and expression profiling. BRAF  mutation, which constitutively activates the mitogen-activated protein kinase (MAPK) pathway, is one of the most common oncogenic mutations in human cancer. Approximately 10% of pediatric HGG will have BRAF mutations. Given the clinical success of the MAPK pathway inhibitors as both monotherapy and in combination for metastatic melanoma with BRAF mutations, this study is being conducted to evaluate dabrafenib and trametinib in combination after local irradiation for children with BRAF mutant HGG. Our hope is that this combination therapy approach improves event-free and overall survival in this devastating disease.