Binimetinib and Encorafenib for the Treatment of Advanced Solid Tumors With Non-V600E BRAF Mutations (BEAVER)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03839342|
Recruitment Status : Recruiting
First Posted : February 15, 2019
Last Update Posted : July 8, 2020
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumor||Drug: Binimetinib Drug: Encorafenib||Phase 2|
BRAF is a gene in humans that is commonly altered in cancer, resulting in a change to the proteins created from this mutation. These altered proteins interact with a process in the body known as the MAPK (mitogen-activated protein kinase) pathway and promote the growth of cancer. Three classes of BRAF mutations have been identified to understand why some patients respond to treatment and others do not. Class 2 and 3 BRAF mutations have worse overall survival. This study will look at participants in these classes (non-V600E BRAF mutations).
Binimetinib is an oral drug (tablet) that stops the function of MEK (mitogen-activated protein kinase kinase). MEK is a part of the MAPK pathway, so blocking this step helps in stopping the pathway from confinuing to grow the cancer.
Encorafenib is an oral drug (capsule) that stops the function of BRAF V600-mutant kinase, the protein that is produced from a type of BRAF gene mutation. This protein promotes the MAPK pathway so blocking this protein stops the MAPK pathway from growing the cancer.
Patients will visit the clinic up to 2 times every 4 weeks (1 cycle) for tests and procedures while taking the study drugs daily. Procedures will involve review of medication and history, imaging scans, blood sample collection for safety and research purposes, urine collection, ECGs, eye exam, MUGA scans and mandatory and optional tumor biopsies.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Binimetinib and Encorafenib for the Treatment of Advanced Solid Tumors With Non-V600E BRAF Mutations|
|Actual Study Start Date :||June 7, 2019|
|Estimated Primary Completion Date :||September 2021|
|Estimated Study Completion Date :||September 2021|
Experimental: Binimetinib + Encorafenib
Binimetinib and encorafenib are administered orally on a twice daily or once daily schedule, respectively in 28-day cycles. Treatment will continue until it is discontinued due to unacceptable toxicity, clinical or radiological disease progression as per RECIST 1.1, investigator decision, and/or withdrawal of consent.
MEK inhibitor, 45mg oral tablet
BRAF inhibitor, 450mg oral capsule
- Objective response rate defined as per RECIST v1.1. [ Time Frame: 2.5 years ]
- Number of participants with toxicities as per NCI CTCAE v5.0. [ Time Frame: 2.5 years ]
- Disease progression defined as per RECIST v1.1 and monitored throughout the study period. Progression Free Survival defined as time from study registration to disease progression or death from any cause. [ Time Frame: 2.5 years ]
- Disease Control Rate defined in accordance with RECIST v1.1, as the percentage of patients who achieve a complete response, partial response or stable disease after 24 weeks of treatment. [ Time Frame: 2.5 years ]
- Overall survival measured as the length of time from the first day of treatment to the day of death. Median OS will be reported. [ Time Frame: 2.5 years ]
- Change in circulating tumor DNA (ctDNA) profiles measured by serial analysis of ctDNA profiles at baseline, mid-cycle 1, with each subsequent cycle, and at progression, validated by comparison to molecular profiles of corresponding fresh tumor biopsies [ Time Frame: 2.5 years ]
- Number of fresh tumor biopsies collected, frozen, and stored for subsequent development of patient derived xenografts. [ Time Frame: 2.5 years ]
- Number of identified molecular mechanisms of acquired resistance to binimetinib and encorafenib in tumors with non-V600E BRAF mutations, measured by analysis of molecular profiles and validated with PDX models in vitro and in vivo. [ Time Frame: 2.5 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03839342
|Contact: Celeste Yu, MSc||416-946-4501 ext email@example.com|
|Princess Margaret Cancer Centre||Recruiting|
|Toronto, Ontario, Canada, M5G2M9|
|Principal Investigator:||Anna Spreafico, MD||Princess Margaret Cancer Centre|