SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03973918

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

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

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.

NCT03973918 High Grade Glioma BRAF V600E BRAF V600K Anaplastic Astrocytoma Anaplastic Pleomorphic Xanthoastrocytoma Gliosarcoma Glioblastoma
MeSH: Glioblastoma Glioma Astrocytoma Gliosarcoma Brain Neoplasms
HPO: Astrocytoma Brain neoplasm Glioblastoma multiforme Glioma Subependymal giant-cell astrocytoma

4 Interventions

Name: Encorafenib

Description: 450mg QD 28 day cycle

Type: Drug

Treatment 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 cycle

Type: Drug

Treatment 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 Treatment

Type: Biological

Treatment 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 slides

Type: Biological

Surgical Arm


Primary Outcomes

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 year

Secondary Outcomes

Description: 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 year

Description: median overall survival

Measure: Overall Survival

Time: up to 2 years

Description: 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 year

Measure: Number of participants with adverse events as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0)

Time: 1 year

Purpose: Treatment

Allocation: Non-Randomized

Parallel Assignment


There are 2 SNPs

SNPs


1 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 ---

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 ---


2 V600K

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 ---



HPO Nodes


HPO:
Astrocytoma
Genes 14
NF2 APC MLH1 CDKN2A MSH6 ERBB2 TSC1 TSC2 PMS2 MSH2 MSH3 IDH1 IDH2 NF1
Brain neoplasm
Genes 7
POLD1 POLE RELA APC RB1 FLI1 C11ORF95
Glioblastoma multiforme
Genes 16
PMS1 APC MLH1 KRAS EPCAM TGFBR2 PIK3CA MSH6 ERBB2 RPS20 BMPR1A PMS2 MSH2 MLH3 SEMA4A FAN1
Glioma
Genes 30
CHEK2 PMS1 APC MLH1 CDKN2A KRAS TGFBR2 LRP5 NBN MSH6 C11ORF95 ERBB2 RPS20 TSC1 BMPR1A TSC2 RELA PMS2 MSH2 MSH3 MLH3 IDH1 IDH2 SEMA4A NF1 NF2 EPCAM PIK3CA SETBP1 FAN1
Subependymal giant-cell astrocytoma
Genes 2
TSC1 TSC2