A Trial of Dabrafenib, Trametinib and Hydroxychloroquine for Patients With Recurrent LGG or HGG With a BRAF Aberration

Running, not enrolling · Phase 1/Phase 2

Conditions studied: Low Grade Glioma (LGG) of Brain With BRAF Aberration, High Grade Glioma (HGG) of the Brain With BRAF Aberration, Low Grade Glioma of Brain With Neurofibromatosis Type 1

In brief

This phase I/II trial is designed to study the side effects, best dose and efficacy of adding hydroxychloroquine to dabrafenib and/or trametinib in children with low grade or high grade brain tumors previously treated with similar drugs that did not respond completely (progressive) or tumors that came back while receiving a similar agent (recurrent). Patients must also have specific genetic mutations including BRAF V600 mutations or BRAF fusion/duplication, with or without neurofibromatosis type 1. Neurofibromatosis type 1 is an inherited genetic condition that causes tumors to grow on nerve tissue. Hydroxychloroquine, works in different ways to stop the growth of tumor cells by killing the cells or stopping them from dividing. Trametinib and dabrafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving hydroxychloroquine with trametinib and/or dabrafenib may lower the chance of brain tumors growing or spreading compared to usual treatments.

Key facts

Study ID

NCT04201457

Run by

Pediatric Brain Tumor Consortium

People needed

57

Starts

2020-01-17

Expected to finish

2026-03-31

Last updated by the study team

2026-02-03

Who can join

Age: 1 and older, up to 30. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• • Patients must have one of the following histologies with molecularly-confirmed diagnosis that is recurrent or progressive. Patients enrolled will be stratified as follows:
• Phase I:
• Stratum 1 LGG or HGG with BRAF V600E/D/K mutation
• Stratum 2 LGG with BRAF duplication or fusion with any partner or LGG with neurofibromatosis type 1
• Phase II:
• Stratum 3 LGG with BRAF V600E/D/K mutation
• Stratum 4 HGG with BRAF V600E/D/K mutation
• Stratum 5 LGG with BRAF duplication or fusion with any partner
• Stratum 6 LGG with neurofibromatosis type 1
• BRAF alterations will be locally determined using molecular methods in a Clinical Laboratory Improvement Act (CLIA)-certified laboratory. Immunohistochemistry for BRAF V600E alone is not adequate and must be confirmed molecularly
• Phase II patients must have bi-dimensionally measurable disease defined as at least one lesion that can be accurately measured in at least two planes. A target lesion should be chosen
• Patients are required to have weight >= 9 kg to enroll on any stratum in the Phase I or Phase II
• Phase I only
• Patients enrolled on the 8 mg/kg/day (dose level 1) must have a weight < 90 kg
• Patients enrolled on the 15 mg/kg/day (dose level 2) must have a weight < 80 kg
• Patients enrolled on the 20 mg/kg/day (dose level 3) must have a weight < 68 kg
• Patients must have received prior therapy other than surgery and must have fully recovered from the acute treatment related toxicities (defined as =< grade 1) of all prior chemotherapy, immunotherapy, radiotherapy or any other treatment modality prior to entering this study
• Only applicable to LGG patients on Phase I and all patients on Phase II
• Patients must have received prior RAF and/or MEK inhibitor therapy and meet one of the following criteria:
• Did not experience an objective response (defined as < PR) OR
• Achieved an objective response (CR or PR) but progressed while on active therapy
• HGG patients on Phase I: may be enrolled regardless of prior MEK /RAF treatment
• Imaging must be available for central review to confirm eligibility for LGG patients on the Phase I study and all patients on the Phase II study
• Patients with HGG on the phase I study do not require central imaging review for eligibility
• Patients with LGG on the Phase I study will not require real-time central imaging review, but imaging must be available for retrospective review in case the subject was enrolled at the RP2D and may be counted as part of the phase II study

You may not qualify if…

• • Breast-feeding women are excluded from this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies
• Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient's ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results:
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Patients with NF1 and history of plexiform neurofibroma will be permitted to enroll
• Patients with a previously documented retinal vein occlusion or severe retinopathy
• Presence of active gastrointestinal (GI) disease or other condition (e.g., small bowel or large bowel resection) that will interfere significantly with the absorption of drugs
• Patients who are unable to discontinue prohibited medications or herbal preparations within 7 days of enrollment and 14 days of starting study therapy
• Patients who are receiving any other anti-cancer or investigational drug therapy are ineligible
• Patients with a history of a known hypersensitivity to dabrafenib, trametinib, HCQ, or any of their excipients or compounds of similar chemical or biologic composition
• Prisoners will be excluded from this study.
• Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits or obtain follow-up studies required to assess toxicity to therapy or to adhere to drug administration plan, other study procedures, and study restrictions

Where it is running

• Phoenix Children's Hospital — Phoenix, Arizona, United States
• Children's Hospital Los Angeles — Los Angeles, California, United States
• Lucile Packard Children's Hospital at Stanford University Medical Center — Palo Alto, California, United States
• Children's Hospital Colorado — Aurora, Colorado, United States
• Children's National Medical Center — Washington D.C., District of Columbia, United States
• University of Florida — Gainesville, Florida, United States
• Children's Healthcare of Atlanta — Atlanta, Georgia, United States
• Lurie Children's Hospital-Chicago — Chicago, Illinois, United States
• National Cancer Institute Pediatric Oncology Branch — Bethesda, Maryland, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• Cincinnati Children Hospital Medical Center — Cincinnati, Ohio, United States
• Nationwide Children's Hospital — Columbus, Ohio, United States
• Children's Hospital of Pittsburgh — Pittsburgh, Pennsylvania, United States
• St. Jude Children Research Hospital — Memphis, Tennessee, United States
• Texas Children's Cancer Center — Houston, Texas, United States

Full record on ClinicalTrials.gov

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