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

Conditions

• High Grade Glioma (HGG) of the Brain With BRAF Aberration
• Low Grade Glioma (LGG) of Brain With BRAF Aberration
• Low Grade Glioma of Brain With Neurofibromatosis Type 1

Eligibility Criteria

Sex

ALL

Age

1 Year - 30 Years

Healthy Volunteers

Not accepted

Interventions

• Dabrafenib — DRUG
  Dabrafenib capsule; Dabrafenib Dispersible Tablet
• Trametinib — DRUG
  Tablet; Powder for Oral Solution
• Hydroxychloroquine — DRUG
  Tablet

Study Details

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 Dates

Start date

Jan 17, 2020

Status verified

Feb 2026

Primary completion

Mar 31, 2026

Completion

Mar 31, 2026

Study Design

Enrollment

57 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Phase 1 Stratum 1 BRAF V600E LGG or HGG
  LGG or HGG with BRAF V600E/D/K mutation will receive Dabrafenib, Trametinib and Hydroxychloroquine. All medications are administered orally with Dabrafenib and HCQ given twice a day and Trametinib given once per day at the assigned dose for a 28 day course. Courses may repeat until the patient meets an off treatment criteria.
• Experimental: Phase 1 Stratum 2 BRAF aberration or LGG with NF1
  LGG with BRAF duplication or fusion with any partner or LGG with NF1 will received Trametinib and Hydroxychloroquine. All medications are administered orally with Trametinib given once per day and HCQ give twice per day at the assigned dose for a 28 day course. Courses may repeat until the patient meets an off treatment criteria.
• Experimental: Phase 2 Stratum 3 LGG with BRAF V600 mutation
  LGG with BRAF V600E/D/K mutation will receive Dabrafenib, Trametinib and Hydroxychloroquine. All medications are administered orally with Dabrafenib and HCQ given twice a day and Trametinib given once per day at the recommended Phase 2 dose for a 28 day course. Courses may repeat until the patient meets an off treatment criteria.
• Experimental: Phase 2 Stratum 4 HGG with BRAF V600 mutation
  HGG with BRAF V600E/D/K mutation will receive Dabrafenib, Trametinib and Hydroxychloroquine. All medications are administered orally with Dabrafenib and HCQ given twice a day and Trametinib given once per day at the recommended Phase 2 dose for a 28 day course. Courses may repeat until the patient meets an off treatment criteria
• Experimental: Phase 2 Stratum 5 LGG with BRAF aberration
  LGG with BRAF duplication or fusion with any partner will receive Trametinib and Hydroxychloroquine. All medications are administered orally with Trametinib given once per day and HCQ give twice per day at the recommended Phase 2 dose for a 28 day course. Courses may repeat until the patient meets an off treatment criteria.
• Experimental: Phase 2 Stratum 6 LGG with NF Type 1
  LGG with Neurofibromatosis Type 1 will receive Trametinib and Hydroxychloroquine. All medications are administered orally with Trametinib given once per day and HCQ give twice per day at the recommended Phase 2 dose for a 28 day course. Courses may repeat until the patient meets an off treatment criteria.

Primary Outcome Measure

Maximum Tolerated Dose (MTD)/ Recommended Phase 2 Dose (RP2D) [ Time Frame: Approximately 28 days from start of therapy ]

Locations (15)

Find similar trials in Phoenix, AZ

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