NCT03973918

Study of Binimetinib With Encorafenib in Adults With Recurrent BRAF V600-Mutated HGG

A Phase II Study of Binimetinib in Combination With Encorafenib in Adults With Recurrent BRAF V600-Mutated High-Grade Astrocytoma or Other Primary Brain Tumor

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this study is to estimate the efficacy of encorafenib and binimetinib as measured by radiographic response in recurrent high-grade primary brain tumors.

Detailed description

Primary Objective Estimate the efficacy of combination treatment with encorafenib and binimetinib, as measured by response rate (RANO criteria), in patients with recurrent BRAF V600E/K-mutated malignant glioma (MG) and anaplastic pleomorphic xanthoastrocytoma (PXAs). Secondary Objectives 1. Estimate efficacy as measured by progression-free survival in subjects with recurrent malignant glioma or anaplastic PXA containing a BRAF-V600E/K mutation who receive drug. 2. Evaluate duration of response in subjects who have a partial or complete response. 3. Quantify the time-to-response among subjects who have a radiologic response. 4. Estimate efficacy as measured by overall survival in subjects with recurrent malignant glioma or anaplastic PXA containing a BRAF-V600E/K mutation who receive drug. 5. Characterize the toxicity profile of the combination of encorafenib and binimetinib in this patient population. There are two arms: medical and surgical. Subjects on the surgical arm must have a high-grade glioma or a known BRAF-mutated low-grade glioma with high clinical suspicion for progression to high-grade. Medical: Following enrollment, patients will receive encorafenib and binimetinib at the FDA-approved dose of 450 mg of encorafenib once daily and the FDA-approved dose of 45 mg of binimetinib twice daily separated by 12 hours, continuously in 28-day cycles until progression or unacceptable toxicity. Patients will be followed by routine blood work, and general and neurological examination. A brain MRI will be performed prior to every odd-numbered cycle (every 8 weeks). Response will be assessed by RANO criteria. Patients may remain on study and receive treatment until progression or other reason. Surgical: These subjects will take encorafenib and binimetinib in combination at their FDA-approved doses for 10-14 days prior to surgery. The last dose of both drugs will be administered two hours prior to surgery. Specimens will be collected during surgery. After surgery, the subjects will not take further encorafenib or binimetinib until a study visit to assess their neurological exam, physical exam, and performance status, at 2-6 weeks post-operatively. At time of restarting combination treatment, subjects will follow the schedule for the medical cohort, and will continue treatment until progression.

Conditions

• High Grade Glioma
• BRAF V600E
• BRAF V600K
• Anaplastic Astrocytoma
• Anaplastic Pleomorphic Xanthoastrocytoma
• Gliosarcoma
• Glioblastoma

Interventions

Type	Name	Description
DRUG	Encorafenib	450mg QD 28 day cycle
DRUG	Binimetinib	45mg BID 28 day cycle
BIOLOGICAL	Research Bloods	Baseline; pre-cycle 3; Pre-cycle 7; off Treatment
BIOLOGICAL	Tumor Tissue	at time of surgery contrast enhancing and non enhancing tumor; 20 unstained slides

Timeline

• Start date: 2019-07-29
• Primary completion: 2022-04-30
• Completion: 2023-10-01
• First posted: 2019-06-04
• Last updated: 2024-10-31
• Results posted: 2024-03-06

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study