Dabrafenib and Trametinib for BRAF V600 Mutant Low-Grade Gliomas

ConditionsBRAF V600 Mutation Low-grade Glioma Low Grade Glioma of Brain Recurrent Low Grade Glioma

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age12-25

SponsorUniversity of California, San Francisco

About this trial

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.

Eligibility criteria

Qualifiers

Participants must have histologically confirmed LGG World Health Organization (WHO) Grade I or II with BRAF V600 mutation confirmed by immunohistochemistry or sequencing

Participants must have measurable tumor.

Participants must have no prior therapy, except for surgical intervention (i.e. biopsy or resection)

Participants may currently be taking dabrafenib and trametinib as frontline therapy, with a maximum duration of 21 months and participants must not yet have met criteria for confirmed best response as defined in this protocol. For participants entering the trial currently taking dabrafenib and trametinib, they must be taking a dose that is within 20% of the standard dosing for both drugs based on age and weight. Participants who are already on dabrafenib and trametinib when enrolling on trial and whose dosing deviates more than 20% from the protocol nomogram need to be discussed with the study chairs. Eligibility for these participants will be based on ability to wean within the parameters of the protocol

Disqualifiers

Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) mutation

Histone H3 mutation (p.K28M, p.G35R, p.G35V)

Neurofibromatosis Type 1 (NF-1) loss of function alteration

Participants who are receiving any other investigational agents

Trial design

Treatments tested in this trial

Dabrafenib
Trametinib
Magnetic Resonance Imaging (MRI)
Specimen Collection
Optional Lumbar puncture

Treatment groups

96 Participants

are divided into 4 treatment groups

Sponsors and collaborators

University of California, San Francisco

Lead sponsor

Rising Tide Foundation

Collaborator

Source ClinicalTrials.gov