Dabrafenib and Trametinib for BRAF V600 Mutant Low-Grade Gliomas

PRIMARY OBJECTIVE: I. To determine if there is a difference in rate of rebound and/or clinical progression necessitating the reinstitution of treatment at 4 months after stopping or weaning therapy with dabrafenib mesylate (dabrafenib) and trametinib dimethyl sulfoxide (trametinib) in participants with newly diagnosed or recurrent/progressive LGGs with BRAF V600 mutation. EXPLORATORY OBJECTIVES: I. To describe the toxicity in participants in different phases of drug administration: Ia. Standard dosing schedule of dabrafenib and trametinib. Ib. Abruptly stopping dabrafenib and trametinib. Ic. Weaning dabrafenib and trametinib. II. To assess the time to rebound and/or radiologic or clinical progression for participants who abruptly stop dabrafenib and trametinib versus participants who wean dabrafenib and trametinib. III. To determine the durability of response, defined as time to progression, for patients treated until confirmed best response or for a maximum of 24 months. IV. To monitor response/toxicity by profiling cell-free deoxyribonucleic acid (DNA) (cfDNA) whole genomes in longitudinal blood and cerebrospinal fluid (CSF) specimens. V. To correlate response/toxicity based on pharmacogenomics. VI. To explore response-predictive features in tumor cellular composition and tissue architecture through multi-dimensional data integration (single nucleus multiomics, spatial tumor tissue profiling, digital pathology). VII. To assess radiogenomic prediction models. VIII. To assess machine learning imaging models accuracy in evaluating response and compare to standard Response Assessment in Neuro-Oncology Low Grade Glioma (RANO-LGG) and Response Assessment in Pediatric Neuro-Oncology (RAPNO)-LGG criteria. IX. To describe the microbiome profile in participants receiving dabrafenib and trametinib. X. To characterize cutaneous toxicities across participants with different skin colors taking a weaning regimen of dabrafenib and trametinib compared to participants taking standard dose dabrafenib and trametinib. OUTLINE: Participants receive dabrafenib and trametinib each cycle for a minimum of 12 cycles and up to a maximum of 24 cycles in the absence of disease progression or unacceptable toxicity. Participants are then randomized to 1 of 2 arms. ARM A: Participants stop treatment with dabrafenib and trametinib. ARM B: Participants receive dabrafenib PO BID and trametinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then up to 5 years.