NCT03919071|Active Not RecruitingPhase 2FDA Drug

Dabrafenib Combined With Trametinib After Radiation Therapy in Treating Patients With Newly-Diagnosed High-Grade Glioma

A Phase 2 Study of Dabrafenib (NSC# 763760) With Trametinib (NSC# 763093) After Local Irradiation in Newly-Diagnosed BRAF V600-Mutant High-Grade Glioma (HGG)

National Cancer Institute (NCI)ClinicalTrials.gov

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3 other identifiers

NCI-2019-02289ACNS1723U10CA180886

Study Type

interventional

Target

Locations

2 countries

Sites

131

Timeline

RegisteredApr 2019

StartedFeb 2020

CompletionSep 2027

Brief Summary

This phase II trial studies how well the combination of dabrafenib and trametinib works after radiation therapy in children and young adults with high grade glioma who have a genetic change called BRAF V600 mutation. Radiation therapy uses high energy rays to kill tumor cells and reduce the size of tumors. Dabrafenib and trametinib may stop the growth of tumor cells by blocking BRAF and MEK, respectively, which are enzymes that tumor cells need for their growth. Giving dabrafenib with trametinib after radiation therapy may work better than treatments used in the past in patients with newly-diagnosed BRAF V600-mutant high-grade glioma.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P25-P50 for phase_2

Timeline

17mo left

Started Feb 2020

Longer than P75 for phase_2

Geographic Reach

2 countries

131 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

7.6 years study duration

Study Progress82%

Feb 2020Sep 2027

First Submitted

Initial submission to the registry

April 17, 2019

Completed

1 day until next milestone

First Posted

Study publicly available on registry

April 18, 2019

Completed

10 months until next milestone

Study Start

First participant enrolled

February 20, 2020

Completed

7.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 30, 2027

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 30, 2027

Last Updated

May 4, 2026

Status Verified

January 1, 2026

Enrollment Period

7.6 years

First QC Date

April 17, 2019

Last Update Submit

May 1, 2026

Conditions

Anaplastic Astrocytoma, Not Otherwise Specified Anaplastic Ganglioglioma Anaplastic Pleomorphic Xanthoastrocytoma Glioblastoma Malignant Glioma WHO Grade 3 Glioma WHO Grade 4 Glioma Anaplastic Astrocytoma

Outcome Measures

Primary Outcomes (1)

Event-free survival (EFS) for stratum 1
The EFS curve for the new treatment cohort (stratum 1) will be estimated by Kaplan Meier estimates. A 2-sample, 1 sided log-rank test will be used to test whether the EFS distribution is better in new treatment compared with historical control. Calculation of the EFS will be based on the site determination as central review will be performed retrospectively.
From the date of diagnosis until disease progression date, secondary malignant neoplasm occurrence date, death date of any cause, or last follow-up, assessed up to 5 years

Secondary Outcomes (3)

Overall survival (OS) for stratum 1, stratum 2, and stratum 3
From the date of diagnosis until death date of any cause or last follow up date, assessed up to 5 years
Event-free survival (EFS) for stratum 2 and stratum 3
Follow up date, assessed up to 5 years
Incidence of adverse events
Up to 5 years

Study Arms (1)

Treatment (radiation therapy, dabrafenib, trametinib)

EXPERIMENTAL

Patients undergo standardized local RT 5 days a week (Monday-Friday) for 6-7 weeks. Four weeks after completion of RT, patients receive dabrafenib mesylate PO BID and trametinib dimethyl sulfoxide PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI at baseline, on day 1 of cycles 1, 3, 5, 7, 11, 14, 17, 20, and 23 while on treatment, then at time of relapse, every 3 months for year 1, every 4 months for year 2, every 6 months for year 3, and annually for years 4-5. Patients may also undergo lumbar puncture for CSF testing during treatment. Patients also undergo collection of blood on study.

Procedure: Biospecimen CollectionDrug: Dabrafenib MesylateProcedure: Lumbar PunctureProcedure: Magnetic Resonance ImagingRadiation: Radiation TherapyDrug: Trametinib Dimethyl Sulfoxide

Interventions

Dabrafenib MesylateDRUG

Given PO

Also known as: Dabrafenib Methanesulfonate, GSK2118436 Methane Sulfonate Salt, GSK2118436B, Tafinlar