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Kinase Inhibitor

Dabrafenib + Trametinib + Hydroxychloroquine for Brain Tumor

Phase 1 & 2

Recruiting

Research Sponsored by Pediatric Brain Tumor Consortium

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have weight >= 9 kg to enroll in Phase I or Phase II

Sexually active males must use a condom and agree not to father a child

Timeline

Screening 3 weeks

Treatment Varies

Follow Up approximately 2 years from start of therapy

Awards & highlights

Study Summary

This trial is designed to study the side effects and efficacy of adding hydroxychloroquine to dabrafenib and/or trametinib in children with brain tumors that have progressed or returned while receiving a similar agent.

Who is the study for?

This trial is for children with low or high grade brain tumors that have specific genetic mutations (BRAF V600, BRAF fusion/duplication) and may include those with neurofibromatosis type 1. Participants must have tried similar treatments without success, be in good health otherwise, not pregnant or breastfeeding, able to use contraception if applicable, and understand the study.Check my eligibility

What is being tested?

The trial tests combining hydroxychloroquine with dabrafenib and/or trametinib to see if it's more effective at stopping tumor growth than current treatments. It's a phase I/II trial which means they're looking for the safest dose that works best against these types of brain tumors.See study design

What are the potential side effects?

Possible side effects include issues affecting blood cells leading to increased infection risk or bleeding problems; liver, kidney or heart problems; eye issues; digestive disturbances; skin reactions; muscle weakness; headaches and potential interactions with other medications.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I weigh at least 9 kg.

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I am a sexually active male and will use a condom to prevent fathering a child.

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My neurological condition is stable and any seizures are under control.

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My blood, liver, kidney, and heart functions meet the required levels.

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I can do most activities but may need help.

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My cancer has returned or worsened and has a specific genetic makeup.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ approximately 2 years from start of therapy

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~approximately 2 years from start of therapy

This trial's timeline: 3 weeks for screening, Varies for treatment, and approximately 2 years from start of therapy for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Area under the curve (AUC)

Maximum Plasma Concentration

Maximum Tolerated Dose (MTD)/ Recommended Phase 2 Dose (RP2D)

+1 more

Secondary outcome measures

Phase I and II: Autophagy inhibition as assessed by the accumulation of LC3II in peripheral blood mononuclear cells

Phase I and II: Autophagy inhibition as assessed by the accumulation of p62 in peripheral blood mononuclear cells

Phase I and II: Presence of MAPK pathway aberrations (other than BRAF) as assessed by whole exome sequencing

+5 more

Trial Design

6Treatment groups

Experimental Treatment

Group I: Phase 2 Stratum 6 LGG with NF Type 1Experimental Treatment2 Interventions

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.

Group II: Phase 2 Stratum 5 LGG with BRAF aberrationExperimental Treatment2 Interventions

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.

Group III: Phase 2 Stratum 4 HGG with BRAF V600 mutationExperimental Treatment3 Interventions

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

Group IV: Phase 2 Stratum 3 LGG with BRAF V600 mutationExperimental Treatment3 Interventions

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.

Group V: Phase 1 Stratum 2 BRAF aberration or LGG with NF1Experimental Treatment2 Interventions

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.

Group VI: Phase 1 Stratum 1 BRAF V600E LGG or HGGExperimental Treatment3 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Hydroxychloroquine

2017

Completed Phase 4

~5360

Dabrafenib

2011

Completed Phase 3

~4120

Trametinib

2014

Completed Phase 2

~1550

0 / 6Eligibility criteria met

Find a Location

Who is running the clinical trial?

National Cancer Institute (NCI)NIH

13,662 Previous Clinical Trials

40,925,998 Total Patients Enrolled

American Lebanese Syrian Associated Charities (ALSAC)UNKNOWN

8 Previous Clinical Trials

610 Total Patients Enrolled

Pediatric Brain Tumor ConsortiumLead Sponsor

37 Previous Clinical Trials

1,507 Total Patients Enrolled

Media Library

Dabrafenib (Kinase Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT04201457 — Phase 1 & 2

High Grade Glioma of the Brain Research Study Groups: Phase 2 Stratum 3 LGG with BRAF V600 mutation, Phase 1 Stratum 1 BRAF V600E LGG or HGG, Phase 1 Stratum 2 BRAF aberration or LGG with NF1, Phase 2 Stratum 4 HGG with BRAF V600 mutation, Phase 2 Stratum 6 LGG with NF Type 1, Phase 2 Stratum 5 LGG with BRAF aberration

High Grade Glioma of the Brain Clinical Trial 2023: Dabrafenib Highlights & Side Effects. Trial Name: NCT04201457 — Phase 1 & 2

Dabrafenib (Kinase Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT04201457 — Phase 1 & 2

Frequently Asked Questions

These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

Does this research endeavor accept geriatric participants?

"This clinical trial is looking to enrol individuals who are between 1 and 30 years of age."

Answered by AI

What is the prime goal of this research endeavor?

"This clinical trial will assess various outcomes over a 28 day period, with the primary goal being to determine sustained objective response rate. Secondary objectives include measuring visual outcome based on Teller Grating Acuity at 55 cm in the left eye for those with tumor-inflicted vision impairment, determining proportion of patients who achieve partial or complete response among those with measurable disease and assessing autophagy inhibition through accumulation of LC3II in peripheral blood mononuclear cells."

Answered by AI

Are there opportunities at present to join this clinical research?

"Affirmative. According to clinicaltrials.gov, this medical trial - first posted in November of 2019 - is currently recruiting 75 willing participants across 15 different sites. The data was most recently updated on November 15th 2022."

Answered by AI

Is it feasible for me to become a participant in this investigation?

"This clinical trial seeks to enroll 75 children between 1 and 30 years of age diagnosed with Watson Syndrome. To qualify, patients must have bi-dimensional measurable disease—at least one lesion that can be accurately measured in two planes—and weigh nine kilograms or more. Additionally, a target lesion should be identified upon enrollment."

Answered by AI

How many individuals are in the scope of this clinical experiment?

"This medical trial requires 75 participants, who meet the designated inclusion criteria, to be recruited. Potential study subjects have multiple locations from which they can enroll in this experiment such as Nationwide Children's Hospital of Columbus, Ohio and Children's Healthcare of Atlanta based in Georgia."

Answered by AI

What diseases has Dabrafenib been demonstrated to ameliorate?

"Dabrafenib is frequently prescribed to treat lupus erythematosus, discoid. It may also be an effective therapy for systemic lupus erythematosus, malaria and q fever."

Answered by AI

Have any other research initiatives explored the possibilities of Dabrafenib?

"The initial research on dabrafenib was conducted in 2007 by the University of Nebraska Medical Center. Subsequently, 218 trials have been concluded and presently there are 155 active studies taking place -- many of which occur at a Columbus, Ohio-based facility."

Answered by AI

In what regions is this clinical evaluation currently being conducted?

"The primary sites for this medical study are Nationwide Children's Hospital in Columbus, Ohio, Children's Healthcare of Atlanta in Atlanta Georgia and Lucile Packard Children's Hospital at Stanford University Medical Center in Palo Alto, California. Additionally there are an additional 15 locations participating."

Answered by AI

Recent research and studies

clinicaltrials.govStudy

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

2020. "A Trial of Dabrafenib, Trametinib and Hydroxychloroquine for Patients With Recurrent LGG or HGG With a BRAF Aberration". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04201457.

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