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.
Name: Encorafenib
Description: 450mg QD 28 day cycleType: DrugTreatment Cohort 1 AA Treatment Cohort 1 AA & Treatment Cohort 1 AA & GBM Treatment Cohort 2 anaplastic PXAs Surgical Arm Treatment Cohort 3 Other Tumors
Name: Binimetinib
Description: 45mg BID 28 day cycleType: DrugTreatment Cohort 1 AA Treatment Cohort 1 AA & Treatment Cohort 1 AA & GBM Treatment Cohort 2 anaplastic PXAs Surgical Arm Treatment Cohort 3 Other Tumors
Name: Research Bloods
Description: Baseline; pre-cycle 3; Pre-cycle 7; off TreatmentType: BiologicalTreatment Cohort 1 AA Treatment Cohort 1 AA & Treatment Cohort 1 AA & GBM Treatment Cohort 2 anaplastic PXAs Surgical Arm Treatment Cohort 3 Other Tumors
Name: Tumor Tissue
Description: at time of surgery contrast enhancing and non enhancing tumor; 20 unstained slidesType: BiologicalSurgical Arm
Description: Number of participants from each treatment cohort with response as defined by Response Assessment in Neuro-oncology (RANO) criteria: Complete Response (CR)= no change in size of T1-gadolinium-enhancing (T1-Gd+) disease, stable or reduced T2/FLAIR signal, no new lesion, no corticosteroid use, and stable or improved clinical status; Partial Response (PR)= ≥50% change in size of T1-Gd+ disease, stable or reduced T2/FLAIR signal, no new lesion, stable or reduced corticosteroid use, and stable or improved clinical status; Stable Disease (SD)= <50% reduction to <25% increase size of T1-Gd+ disease, stable or reduced T2/FLAIR signal, no new lesion, stable or reduced corticosteroid use, and stable or improved clinical status; Progressive Disease (PD)= ≥25% increase size of T1-Gd+ disease, or increased T2/FLAIR signal, or presence of new lesion, or worsening clinical status.
Measure: Tumor radiographic response per RANO for 3 treatment cohorts Time: 1 yearDescription: Progressive Disease (PD)= ≥25% increase size of T1-Gd+ disease, or increased T2/FLAIR signal, or presence of new lesion, or worsening clinical status
Measure: Progression free survival for 3 treatment cohorts Time: up to 1 yearDescription: median overall survival
Measure: Overall Survival Time: up to 2 yearsDescription: Time from response to progression. Response is defined by RANO: Complete Response (CR)= no change in size of T1-gadolinium-enhancing (T1-Gd+) disease, stable or reduced T2/FLAIR signal, no new lesion, no corticosteroid use, and stable or improved clinical status; Partial Response (PR)= ≥50% change in size of T1-Gd+ disease, stable or reduced T2/FLAIR signal, no new lesion, stable or reduced corticosteroid use, and stable or improved clinical status; Stable Disease (SD)= <50% reduction to <25% increase size of T1-Gd+ disease, stable or reduced T2/FLAIR signal, no new lesion, stable or reduced corticosteroid use, and stable or improved clinical status; Progressive Disease (PD)= ≥25% increase size of T1-Gd+ disease, or increased T2/FLAIR signal, or presence of new lesion, or worsening clinical status.
Measure: Duration of response Time: up to 1 yearAllocation: Non-Randomized
Parallel Assignment
There are 2 SNPs
High Grade Glioma BRAF V600E BRAF V600K Anaplastic Astrocytoma Anaplastic Pleomorphic Xanthoastrocytoma Gliosarcoma Glioblastoma Glioblastoma Glioma Astrocytoma Gliosarcoma Brain Neoplasms 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). --- V600E ---
High Grade Glioma BRAF V600E BRAF V600K Anaplastic Astrocytoma Anaplastic Pleomorphic Xanthoastrocytoma Gliosarcoma Glioblastoma Glioblastoma Glioma Astrocytoma Gliosarcoma Brain Neoplasms 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). --- V600E --- --- V600K --- --- V600E ---
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. --- V600E ---
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. --- V600E ---
High Grade Glioma BRAF V600E BRAF V600K Anaplastic Astrocytoma Anaplastic Pleomorphic Xanthoastrocytoma Gliosarcoma Glioblastoma Glioblastoma Glioma Astrocytoma Gliosarcoma Brain Neoplasms 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). --- V600E --- --- V600K ---