RecruitingBRAF V600 MutationLow-grade GliomaLow Grade Glioma of Brain

Dabrafenib and Trametinib for BRAF V600 Mutant Low-Grade Gliomas

Eligible age

1–25 yrs

Accepts

All genders

Locations

10 states

Healthy volunteers

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About this study

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.

Sponsor: University of California, San Francisco

You may qualify if…

✓ 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 of radiation therapy. Participants without measurable disease may be considered for enrollment and followed for survival and progression purposes but will not be included as part of a measurable disease cohort.
✓ Cohort 1:
✓ 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
✓ Cohort 2:
✓ \* Participants must have a history of recurrent or progressive disease following prior therapy (e.g., carboplatin and vincristine, vinblastine, bevacizumab, mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor, radiation therapy etc). Participants who previously completed a course of therapy with dabrafenib and trametinib, who did not progress on this therapy, and who are beyond 6 months from completion of therapy are eligible for retreatment.

You may not qualify if…

✕ Participant's tumor has any of the following additional previously known or expected activating molecular alterations:
✕ 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
✕ History of allergic reactions attributed to compounds of similar chemical or biologic composition to dabrafenib and trametinib
✕ Medications that are affected by the induction of CYP3A4 and CYP2C9 should be avoided or used cautiously. Dabrafenib has been shown to induce CYP3A4 and CYP2C9. In addition, dabrafenib is an in vitro inducer of CYP2B6, CYP2C8, CYP2C19, Uridine 5'-diphospho (UDP)-glucuronosyltransferase. Co-administration of dabrafenib and medications which are affected by the induction of these enzymes (including warfarin) and transporters may result in loss of efficacy. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the participant and/or legal parent or guardian will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product
✕ Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection