Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Adenocarcinoma

Colorectal Neoplasms

Rectal Neoplasms

Colonic Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Herbal and Botanical

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Cola

Participants in Phase 1 receive encorafenib PO QD on days 1-28, binimetinib PO BID on days 1-28, and nivolumab IV on day 1. Cycles repeat every 28 days for a maximum of 24 cycles of treatment in the absence of disease progression or unacceptable toxicity.

The study was terminated before Phase II was initiated. The study did not open Phase II for enrollment.

Binimetinib

Encorafenib

Questionnaire Administration

Chloe E Atreya, MD, PhD

This phase I/II trial studies the side effects and how well encorafenib, binimetinib, and nivolumab work in treating patients with microsatellite stable, BRAFV600E gene-mutated colorectal cancer that has spread to other places in the body (metastatic). Encorafenib and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving encorafenib, binimetinib, and nivolumab may work better in treating patients with colorectal cancer compared to standard treatments.

This was intended to be a phase I/II study of Encorafenib, Binimetinib, and Nivolumab for treating participants with Microsatellite Stable BRAF V600E Metastatic Colorectal Cancer. The study was terminated before Phase II was initiated. The study did not open Phase II for enrollment.

PRIMARY OBJECTIVES:

I. To describe overall response rate (ORR) upon treatment with encorafenib, binimetinib, and nivolumab in patients with BRAFV600E, microsatellite stable (MSS) metastatic colorectal cancer (mCRC).

II. To determine the safety and tolerability of nivolumab, encorafenib, and binimetinib in patients with BRAFV600E, MSS mCRC.

SECONDARY OBJECTIVES:

I. To estimate median progression-free survival (PFS) upon treatment with encorafenib, binimetinib, and nivolumab.

II. To estimate median overall survival (OS) upon treatment with encorafenib, binimetinib, and nivolumab.

III. To estimate median time to response (TTR) upon treatment with encorafenib, binimetinib, and nivolumab.

IV. To estimate median duration of response (DoR) upon treatment with encorafenib, binimetinib, and nivolumab.

V. To estimate disease control rate (DCR) upon treatment with encorafenib, binimetinib, and nivolumab.

EXPLORATORY (CORRELATIVE) OBJECTIVES:

I. To assess genomic and immune changes upon treatment with encorafenib, binimetinib, and nivolumab in tumor tissue, blood and stool.

II. To correlate genomic and immune changes upon treatment with encorafenib, binimetinib, and nivolumab in tumor tissue, blood and stool with radiographic response.

III. To evaluate contrast-enhanced computed tomography (CT) imaging for disease burden that is not measurable by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) and to correlate location and patterns of metastatic disease with clinical outcomes.

OUTLINE:

Participants in received encorafenib orally (PO) once daily (QD) on days 1-28, binimetinib PO twice daily (BID) on days 1-28, and nivolumab intravenously (IV) on day 1. Cycles repeat every 28 days for a maximum of 24 cycles of treatment. If disease progression or recurrence occurs, treatment may be resumed outside of the context of the clinical trial.

After completion of study treatment, patients are followed up at 30 and 100 days, then every 3 months thereafter.

Only participants in Phase 1 were enrolled.

Encorafenib, Binimetinib, and Nivolumab in Treating Microsatellite Stable BRAF V600E Metastatic Colorectal Cancer

Phase I/II Trial of Encorafenib, Binimetinib, and Nivolumab in Microsatellite Stable BRAF V600E Metastatic Colorectal Cancer

Will be measured according to immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). The point estimate of the objective response rate (ORR) and its 95% confidence interval will be obtained.

Will be assessed in the following order of importance: complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), and not evaluable. The point estimate of the ORR and its 95% confidence interval will be obtained

Will be graded according to the Common Terminology Criteria for Adverse Events version 5.0. Safety data will be tabulated.

Will be defined by irRECIST criteria for the evaluable population. Will be estimated by Kaplan-Meier method and summarized with Kaplan-Meier curves and log rank test from start of treatment until death or PD

Will be estimated by Kaplan-Meier method and summarized with Kaplan-Meier curves and log rank test from start of treatment until death occurs

Will be defined by irRECIST criteria. Will be estimated by Kaplan-Meier method and summarized with Kaplan-Meier curves and log rank test from start of treatment until time of response.

Will be estimated by Kaplan-Meier method and summarized with Kaplan-Meier curves and log rank test from first partial or CR to time of PD or death for subjects with a response

The proportion of patients with CR, PR, or SD defined by irRECIST criteria in the evaluable population. The point estimate of DCR and its 95% confidence interval will be obtained.

Pfizer

Bristol-Myers Squibb

University of California, San Francisco

Principal Investigator

Hypoglycemic Agents

Metformin

Patients receive metformin PO BID starting on day 1. After 14 days of metformin only period patients also receive nivolumab IV every 4 weeks starting on day 15. Courses repeat every 28 days for up to 2 years in the absence of disease progression, unacceptable toxicity or consent withdrawal.

Olumide B. Gbolahan, MBBS, MSc

This phase II trial studies how well nivolumab and metformin work in treating patients with microsatellite stable (MSS) stage IV colorectal cancer that has not responded to previous treatment. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Metformin is an antidiabetic drug that and may reduce the risk of colorectal cancer development in patients. Giving nivolumab and metformin may work better in treating patients with refractory microsatellite metastatic colorectal cancer.

PRIMARY OBJECTIVE:

I. To evaluate the effect of nivolumab and metformin combination on the overall response rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

SECONDARY OBJECTIVES:

I. To determine the effect of nivolumab and metformin combination on clinical outcomes, progression free survival and overall survival, and biochemical response (CEA).

II. To compare the effect of nivolumab and metformin combination on immune and metabolic biomarkers in the tumor microenvironment and systemic circulation (pre and post treatment paired biopsies required).

OUTLINE:

Patients receive metformin PO BID starting on day 1. After 14 days of metformin only period patients also receive nivolumab IV every 4 weeks starting on day 15. Courses repeat every 28 days for up to 2 years in the absence of disease progression, unacceptable toxicity or consent withdrawal

After completion of study treatment, patients are followed up at day 30 and then periodically thereafter.

Nivolumab and Metformin in Patients With Treatment Refractory MSS Colorectal Cancer

Phase II Trial of Nivolumab and Metformin in Patients With Treatment Refractory MSS Metastatic Colorectal Cancer

Response will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1., and rate will be calculated as a proportion (responders/total patients).

For progression free survival, progression or death from any cause will be defined as the event. Patients will be censored at time of last follow-up.

For overall survival, death from any cause will be defined as the event. Patients will be censored at time of last follow-up.

Tumor marker carcinoembryonic antigen (CEA) will be assessed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Encorafenib, Binimetinib, and Nivolumab in Treating Microsatellite Stable BRAF V600E Metastatic Colorectal Cancer	NCT04044430	Metastatic Colo... Metastatic Colo... Metastatic Micr... Metastatic Rect... Stage III Colon... Stage III Color... Stage III Recta... Stage IIIA Colo... Stage IIIA Colo... Stage IIIA Rect... Stage IIIB Colo... Stage IIIB Colo... Stage IIIB Rect... Stage IIIC Colo... Stage IIIC Colo... Stage IIIC Rect... Stage IV Colon ... Stage IV Colore... Stage IV Rectal... Stage IVA Colon... Stage IVA Color... Stage IVA Recta... Stage IVB Colon... Stage IVB Color... Stage IVB Recta... Stage IVC Colon... Stage IVC Color... Stage IVC Recta...	Binimetinib Encorafenib Nivolumab Questionnaire A...	18 Years -	University of California, San Francisco
Nivolumab and Metformin in Patients With Treatment Refractory MSS Colorectal Cancer	NCT03800602	Colorectal Aden... Metastatic Micr... Refractory Colo... Stage IV Colore... Stage IVA Color... Stage IVB Color... Stage IVC Color... Colorectal Canc...	Metformin Nivolumab	18 Years -	Emory University

Spots Global Cancer Trial Database for stage ivc colorectal cancer