A Trial of Dabrafenib, Trametinib and Hydroxychloroquine for Patients With Recurrent LGG or HGG W… (NCT04201457) | Clinical Trial Compass
Active — Not RecruitingPhase 1/2
A Trial of Dabrafenib, Trametinib and Hydroxychloroquine for Patients With Recurrent LGG or HGG With a BRAF Aberration
United States57 participantsStarted 2020-01-17
Plain-language summary
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.
Who can participate
Age range
1 Year – 30 Years
Sex
ALL
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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion Criteria:
* • 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 ful…
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1This trial is combining dabrafenib, trametinib, and hydroxychloroquine — three drugs together — so what is currently known about the safety profile of this specific combination, and what side effects should I be most concerned about given that the Phase 1 part is still identifying the safest dose?
2Since the trial is listed as 'active not recruiting,' does that mean enrollment is closed, and if so, are there other trials or standard treatment options targeting my BRAF aberration that my care team would recommend instead?
3The trial is measuring something called a 'sustained objective response rate' in Phase 2 — what does that mean in practical terms for someone with my type of glioma, and how does that compare to what I might expect from currently approved BRAF-targeted treatments?
4Because this is a Phase 1/2 trial still working out the right dose, how does that affect what is and isn't known about whether this combination would be more beneficial than the standard approaches my team might already be considering for my recurrent glioma?
5Hydroxychloroquine is typically used for other conditions like autoimmune disease — can you help me understand why it's being added to the BRAF and MEK inhibitors in this trial, and what that might mean for my day-to-day life while on treatment?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Maximum Tolerated Dose (MTD)/ Recommended Phase 2 Dose (RP2D)
Timeframe: Approximately 28 days from start of therapy
2
Maximum Plasma Concentration
Timeframe: 1-4 days
3
Area under the curve (AUC)
Timeframe: 1-4 days
4
Phase II: Sustained objective response rate.
Timeframe: Up to approximately 2 years from the start of therapy