NCT07110246

Dabrafenib and Trametinib for BRAF V600 Mutant Low-Grade Gliomas

A Phase 2 De-escalation Study of Dabrafenib and Trametinib for Patients With BRAF V600 Mutant Low-Grade Gliomas

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 96 (estimated)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: All
• Age: 12 Months – 25 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies how well de-escalating the drugs dabrafenib and trametinib works in treating patients with low-grade gliomas that have a BRAF V600 gene mutation. Dabrafenib and trametinib are in a class of medications called kinase inhibitors. They work by blocking the action of abnormal proteins that signals tumor cells to multiply. This helps stop the spread of tumor cells. This trial may help doctors determine the best dosing strategy for patients who have received dabrafenib and trametinib for 12-24 months: Either stopping dabrafenib and trametinib completely or slowly reducing the dose for an additional 6 months.

Detailed description

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.

Conditions

• BRAF V600 Mutation
• Low-grade Glioma
• Low Grade Glioma of Brain
• Recurrent Low Grade Glioma

Interventions

Type	Name	Description
DRUG	Dabrafenib	Given orally (PO)
DRUG	Trametinib	Given PO
PROCEDURE	Magnetic Resonance Imaging (MRI)	Undergo imaging by MRI
PROCEDURE	Specimen Collection	Under collection of blood and optional CSF samples
PROCEDURE	Optional Lumbar puncture	Undergo optional lumbar puncture

Timeline

• Start date: 2025-11-07
• Primary completion: 2032-03-31
• Completion: 2032-03-31
• First posted: 2025-08-07
• Last updated: 2026-03-12

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study