A Phase 2 De-escalation Study of Dabrafenib and Trametinib for Patients With BRAF V600 Mutant Low-Grade Gliomas
University of California, San Francisco
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.
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.…
Eligibility
- Age range
- 1–25 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * 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. \* For participants with measurable disease, this will be defined as lesions that can be accurately measured in two dimensions (longest diameter to be recorded) with a minimum size of no less than double the slice thickness. Previously irradiated lesions are considered non-measurable except in cases of documented progression of the lesion since the completion…
Interventions
- DrugDabrafenib
Given orally (PO)
- DrugTrametinib
Given PO
- ProcedureMagnetic Resonance Imaging (MRI)
Undergo imaging by MRI
- ProcedureSpecimen Collection
Under collection of blood and optional CSF samples
- ProcedureOptional Lumbar puncture
Undergo optional lumbar puncture
Locations (5)
- University of Alabama at BirminghamBirmingham, Alabama
- University of California, San FranciscoSan Francisco, California
- John Hopkins Medical CenterBaltimore, Maryland
- St. Louis Children's Hospital Washington University in St. LouisSt Louis, Missouri
- St. Jude Children's Research HospitalMemphis, Tennessee