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Colorectal Neoplasms

Rectal Neoplasms

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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

Nivolumab

Antibodies

Antibodies, Monoclonal

Ipilimumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive regorafenib PO QD on days 1-21, nivolumab IV over 30 minutes Q2W, and ipilimumab IV over 30 minutes Q6W. Cycles repeat every 28 day for up to 2 years in the absence of disease progression or unacceptable toxicity.

Regorafenib

Marwan G Fakih

This phase I trial studies the side effects and best dose of regorafenib when given together with ipilimumab and nivolumab in treating patients with microsatellite stable colorectal cancer that has spread to other places in the body (metastatic) and remains despite chemotherapy treatment (resistant). Regorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as ipilimumab and 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 regorafenib, ipilimumab and nivolumab may slow the tumor growth and/or shrink the tumor size in patients with colorectal cancer.

PRIMARY OBJECTIVE:

I. To determine the recommended dose level of the combination of regorafenib, nivolumab and ipilimumab in patients with advanced metastatic colorectal cancer.

SECONDARY OBJECTIVES:

I. Assess the objective overall response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.

II. Estimate the duration of response, duration of stable disease (SD), progression free survival (PFS), and overall survival (OS).

III. Describe the safety of this regimen as determined by frequency and severity of associated adverse events.

EXPLORATORY OBJECTIVES:

I. Correlate the presence of colony stimulating factor 1 receptor (CSF1R)+ macrophages, regulatory T cells (Tregs), TILs (tumor infiltrating lymphocytes) and tumor PD-L1, CTLA-4 and PD1 expression (at baseline and post treatment) on tumor biopsies with response rate.

II. Characterize the systemic immune alteration through evaluation of mandatory pre and post cycle 1, and cycle 2, and at progression blood draws.

OUTLINE: This is a dose-escalation study of regorafenib.

Patients receive regorafenib orally (PO) once daily (QD) on days 1-21, nivolumab intravenously (IV) over 30 minutes every 2 weeks (Q2W), and ipilimumab IV over 30 minutes every 6 weeks (Q6W). Cycles repeat every 28 day for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 and 90 days, then every 3 months for up to 5 years.

Regorafenib, Ipilimumab and Nivolumab for the Treatment of Chemotherapy Resistant Microsatellite Stable Metastatic Colorectal Cancer

A Phase I Clinical Trial of Regorafenib, Nivolumab, and Ipilimumab in Advanced Chemotherapy Resistant Metastatic MSS Colorectal Cancer

Correlative studies using serial tumor tissue and blood samples will assess immune response at pre-treatment and post-treatment. Will be summarized using exploratory methods. Changes in tumor and blood measurements from pre-treatment to post-treatment will be displayed graphically and summarized with responding individuals identified. Academic standard statistical methods will be used for these exploratory analyses.

Toxicities will be graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v). 5.0. Dose limiting toxicity (DLT) will be graded per CTCAE v5.0. Any of the following adverse events occurring during the primary DLT observation period (4 weeks, from the time of first administration of regorafenib, ipilimumab and nivolumab\[cycle 1 day 1\] until the planned administration of the second cycle of regorafenib (cycle 2 day 1) that are at least probable attributable to many of the 3 agents or their combination will be classified as a DLT.

Assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. Will be summarized using the Kaplan-Meier method.

Assessed using RECIST v 1.1. Duration of response (possibly censored) will be reported for each response.

Assessed using RECIST v 1.1. Will be summarized using the Kaplan-Meier method.

ORR is defined as the percentage of measurable disease participants who have achieved either complete response (CR) or partial response (PR). Assessed using RECIST v 1.1.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Regorafenib, Ipilimumab and Nivolumab for the Treatment of Chemotherapy Resistant Microsatellite Stable Metastatic Colorectal Cancer	NCT04362839	Advanced Colon ... Metastatic Colo... Metastatic Colo... Metastatic Colo... Metastatic Rect... Stage III Colon... Stage III Recta... Stage IIIA Colo... Stage IIIA Rect... Stage IIIB Colo... Stage IIIB Rect... 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...	Ipilimumab Nivolumab Regorafenib	18 Years -	City of Hope Medical Center
Regorafenib, Ipilimumab and Nivolumab for the Treatment of Chemotherapy Resistant Microsatellite Stable Metastatic Colorectal Cancer	NCT04362839	Advanced Colon ... Metastatic Colo... Metastatic Colo... Metastatic Colo... Metastatic Rect... Stage III Colon... Stage III Recta... Stage IIIA Colo... Stage IIIA Rect... Stage IIIB Colo... Stage IIIB Rect... 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...	Ipilimumab Nivolumab Regorafenib	18 Years -	City of Hope Medical Center
Regorafenib, Ipilimumab and Nivolumab for the Treatment of Chemotherapy Resistant Microsatellite Stable Metastatic Colorectal Cancer	NCT04362839	Advanced Colon ... Metastatic Colo... Metastatic Colo... Metastatic Colo... Metastatic Rect... Stage III Colon... Stage III Recta... Stage IIIA Colo... Stage IIIA Rect... Stage IIIB Colo... Stage IIIB Rect... 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...	Ipilimumab Nivolumab Regorafenib	18 Years -	City of Hope Medical Center

Spots Global Cancer Trial Database for advanced colon adenocarcinoma