Dabrafenib and Trametinib for BRAF V600 Mutant Low-Grade Gliomas
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
This trial does not accept healthy volunteersQualifiers
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
Design model
Parallel
Treatments tested in this trial
Dabrafenib
DrugGiven orally (PO)
Trametinib
DrugGiven PO
Magnetic Resonance Imaging (MRI)
Procedure/SurgeryUndergo imaging by MRI
Specimen Collection
Procedure/SurgeryUnder collection of blood and optional CSF samples
Optional Lumbar puncture
Procedure/SurgeryUndergo optional lumbar puncture
Treatment groups
96 Participants
are divided into 4 treatment groupsGroup A: Cohort 1: Arm A (Newly diagnosed, Dabrafenib, Trametinib followed by treatment stop)Experimental treatment 5 interventions
Group B: Cohort 1: Arm B (Newly diagnosed, Dabrafenib, Trametinib followed by weaning)Experimental treatment 5 interventions
Group C: Cohort 2: Arm A (Recurrent LGG, Dabrafenib, Trametinib followed by treatment stop)Experimental treatment 5 interventions
Group D: Cohort 2: Arm B (Recurrent LGG, Dabrafenib, Trametinib followed by weaning)Experimental treatment 5 interventions
Trial outcomes
Primary outcomes
1
Rebound rate (RR)
The Rebound rate is defined as increase in tumor size by 25% or more by Response Assessment in Pediatric Neuro-Oncology-Low Grade Glioma (RAPNO-LGG) criteria and/or clinical progression necessitating the re-institution of therapy occurring within 4 months off therapy for participants with BRAF V600 mutant LGG after abruptly stopping or weaning off dabrafenib and trametinib. RR will be reported by cohort and arm.
Time frame
Up to a maximum of 34 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
University of California, San Francisco
Lead sponsor
Rising Tide Foundation
Collaborator
Source ClinicalTrials.gov