Dabrafenib and Trametinib for BRAF V600 Mutant Low-Grade Gliomas
This study is looking at how to best use the medications dabrafenib and trametinib in children and young adults (ages 12 months to 25 years) with low-grade gliomas (a type of brain tumor) that have a specific gene change called a BRAF V600 mutation. These medications work by blocking signals that help tumor cells grow. The trial aims to find out if it's better to completely stop these medications or slowly reduce the dose after taking them for 12-24 months. To join, you must have a confirmed low-grade glioma with the BRAF V600 mutation and a tumor that can be measured. The study will measure how often the tumor grows back or gets worse after stopping or reducing the medication. The current status of this study is unclear.
- Study design
- This interventional study plans to enroll 96 participants. It is a Phase II trial, but the phase is not specified in the provided information.
- What's involved
- You would take dabrafenib and trametinib by mouth. You would also undergo Magnetic Resonance Imaging (MRI) scans, have blood collected, and potentially have cerebrospinal fluid (CSF) collected through an optional lumbar puncture.
- Compensation
- Not stated in the trial record.
- Follow-up
- The study will measure the rebound rate for up to a maximum of 34 months.
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NCT07110246
Dabrafenib and Trametinib for BRAF V600 Mutant Low-Grade Gliomas
Recruiting
PHASE2Ages 12–25InterventionalTreatmentUniversity of California, San FranciscoInvestigator-initiated
~96 participants
Updated 2026-08-03 on ClinicalTrials.gov
What's tested:DabrafenibTrametinibMagnetic Resonance Imaging (MRI)Specimen CollectionOptional Lumbar puncture
At a glance
Recruiting sites
9 of 9 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Rebound rate (RR)
Measured over Up to a maximum of 34 months
Conditions
Where it's being run
9 sites across 9 statesAlabama1
California1
District of Columbia1
Maryland1
Missouri1
New Jersey1
North Carolina1
Tennessee1
Study leadership
- Sabine Mueller, MD, PHD · PRINCIPAL_INVESTIGATOR · University of California, San Francisco
Who to contact
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Do you actually qualify for this trial?
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Eligibility criteria
Inclusion
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.
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 received their last dose of chemotherapy 3 weeks prior to enrollment (6 weeks for nitrosoureas) and recovered from acute adverse events due to agents administered
Participants must be at least 7 days since the completion of therapy with a biologic or small molecule agent except dabrafenib and trametinib. For any agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur. Such participants must be discussed with study chairs
Radiation:
No prior radiation is allowed for participants in Cohort 1
Participants in Cohort 2 must have:
Had their last fraction of local irradiation to primary tumor ≥ 12 weeks prior to registration
Had their last fraction of craniospinal irradiation ≥ 12 weeks prior to registration
At least 14 days after local palliative radiation (small-port)
Age: ≥ 12 months and \< 25 years old
Performance Score: Karnofsky ≥ 50 for participants \> 16 years of age and Lansky ≥ 50 for participants ≤ 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
Peripheral absolute neutrophil count (ANC) ≥ 1000/mm\^3
Platelet count ≥ 100,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
A serum creatinine ≤ 1.5 upper limit of normal (ULN) based on age and gender
Total bilirubin ≤ 1.5 x ULN for age; in presence of Gilbert's syndrome, total bilirubin ≤ 3 x ULN or direct bilirubin ≤ 1.5 x ULN
Alanine aminotransferase (ALT) ≤ 3 x ULN
Aspartate aminotransferase (AST) ≤ 3 x ULN
Participants with seizure disorder may be enrolled if well controlled
Left ventricular ejection fraction (LVEF) greater than or equal to institutional lower limit of normal (LLN) by echocardiogram (ECHO) (while not receiving medications for cardiac function)
Correct QT (QTc) interval \< 480 msecs
Patient must agree to adequate contraception. (The effects of dabrafenib and trametinib on the developing human fetus are unknown. For this reason and because agents as well as other therapeutic agents used on this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method birth control, or abstinence) prior to study entry, for the duration of study participation, and 4 months after completion of the study medication administration. Should a women become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately)
A legal parent/guardian or patient must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate
Participants must enroll on Pediatric Neuro-Oncology Consortium (PNOC) comprehensive follow up protocol (PNOC COMP) if PNOC COMP is open to accrual at the enrolling institution
Pathology reports, next generation sequencing reports, or both, confirming BRAF V600E mutation status must be submitted at the time of enrollment
Exclusion
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
Women of childbearing potential must not be pregnant or breast-feeding
Human immunodeficiency virus (HIV) positive participants will be ineligible if HIV therapy regimen has not been stable for at least 4 weeks or there is intent to change the regimen within 8 weeks following enrollment, or if they are severely immunocompromised
What this trial measures
- Rebound rate (RR)Up to a maximum of 34 months
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.