3C-14-1: A Phase 2 Clinical Trial of Nivolumab and Nivolumab Plus Ipilimumab in Recurrent and Metastatic Microsatellite High (MSI-H) Colon Cancer
Description
Detailed Description
This is a Phase 2 open-label, multi-center, 2-stage Simon design stage trial of nivolumab (BMS-936558) monotherapy (mStage) or in combination with ipilimumab (cStage) to estimate the response rate in Metastatic Microsatellite MSI-High colon cancer. Ipilimumab is a fully humanized IgG1 monoclonal antibody binding to the anti-cytotoxic T-cell lymphoma-4 antigen (CTLA-4). Ipilimumab is an approved therapy for metastatic melanoma.Nivolumab (BMS-936558; anti-PD-1 mAb) is a fully human monoclonal immunoglobulin (Ig) G4 antibody that binds to the programmed death-1 (PD-1), a negative regulatory molecule expressed by immune cells.Primary Objective of the study is to evaluate the objective response rate (ORR) of nivolumab monotherapy or nivolumab combined with ipilimumab in subjects with metastatic MSI-H colon cancer.The study will also contain a safety cohort of subjects with non-MSI-H colon cancer to assess the safety and tolerability of nivolumab in combination with ipilimumab in subjects with non-MSI-H colon cancerBoth Arms N and N+I will follow a two-stage design to test whether nivolumab monotherapy or nivolumab combined with ipilimumab yields an objective response rate (ORR) that is of clinical interest in MSI-H metastatic colorectal cancer mCRC. On treatment stages that meet an ORR threshold will proceed from Stage 1 to Stage 2 (same for both m and cStage). The primary endpoint of this study ORR which is based on tumor assessments at baseline and then at 6 weeks from first dose and continue every 6 weeks for the first 24 weeks and every 12 weeks thereafter until disease progressionThe study will enroll 96 patients out of which 15 will be enrolled at USC
Phase
Phase 2Inclusion and Exclusion Criteria
- Men and women ≥ 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
- Histologically confirmed colorectal cancer
- Measurable disease by CT or MRI
- Testing for MSI Status
- Adequate organ function as defined by study-specific laboratory tests
- Must use acceptable form of birth control throughout the study. After the final dose of study drug, an acceptable form of birth control must be used for 23 weeks for women of childbearing potential (WOCBP) and 31 weeks for men who are sexually active with WOCBP
- Signed informed consent
- Willing and able to comply with study procedures
- Active brain metastases or leptomeningeal metastases are not allowed.
- Prior treatment with an anti-Programmed Death Receptor (PD)-1, anti-PD-L1, anti-PD-L2, anti-Cytotoxic T-Cell Lymphoma-4 Antigen (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
- Prior malignancy active within the previous 3 years except for locally curable cancers
- Subjects with active, known or suspected autoimmune disease
- Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration
Sites
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California
- Usc Norris Comprehensive Cancer Center, Los Angeles, California, 90033
- Pacific Hematology Oncology Associates, San Francisco, California, 94115
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Arizona
- Local Institution, Gilbert, Arizona, 85234
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Oregon
- Providence Cancer Center Oncology And Hematology Care- Eastside, Portland, Oregon, 97213
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Texas
- The University Of Texas Md Anderson Cancer Center, Houston, Texas, 77030
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Minnesota
- Allina Health, Minneapolis, Minnesota, 55407
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Tennessee
- Vanderbilt-Ingram Cancer Ctr, Nashville, Tennessee, 37232
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Georgia
- Emory University, Atlanta, Georgia, 30322
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