This research is being done to study the effects of the combination of ipilimumab, nivolumab, and radiation therapy in people with metastatic microsatellite stable colorectal cancer. This research study involves the following drugs and interventions: * Ipilimumab * Nivolumab * Radiation Therapy
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied. The U.S. Food and Drug Administration (FDA) has not approved the combination of ipilimumab and nivolumab for metastatic microsatellite stable colorectal cancer but they have been approved for other uses. The FDA has not approved ipilimumab for metastatic microsatellite stable colorectal cancer, but it has been approved for other uses. The FDA has not approved nivolumab for metastatic microsatellite stable colorectal cancer, but it has been approved for other uses. Ipilimumab and Nivolumab are both genetically-engineered antibodies. An antibody is a protein that can attach to specific molecular targets. Ipilimumab and nivolumab work by activating the immune system, which can help to fight certain cancers. This trial explores whether radiation therapy may increase the benefit from immune activation with ipilimumab and nivolumab. The research study procedures include screening for eligibility, and study treatment including evaluations and follow up visits. Participants will be in this research study for as long as the study interventions are safe and beneficial. Participants will then be followed for up to 5 years. It is expected that about 30 people will take part in this research study. Bristol-Myers Squibb, a pharmaceutical company, is supporting this research study by providing funding for this study, including the two study drugs.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
32
Administered into vein by intravenous infusion every 2 weeks over 6 week study cycle.
Administered into vein by intravenous infusion day 1 of each 6 week study cycle.
3 radiation treatments, every other weekday or 2 days during week 1 of cycle 1 only of study.
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Overall response rate for unirradiated lesions (ORR)
Estimate the overall response rate (ORR) for unirradiated lesions for nivolumab/ipilimumab/radiation in metastatic, microsatellite stable colorectal cancer by RECIST 1.1. ORR is the number of patients that achieve either a CR or PR. * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. * Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From the start of the treatment until disease progression/recurrence, up to 5 years
Disease control rate (DCR)
Estimate the disease control rate (DCR) for unirradiated lesions for nivolumab/ipilimumab/radiation in metastatic, microsatellite stable colorectal cancer per Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Disease control is the number of patients that achieve either a CR, PR, or SD. * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. * Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. * Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study.
Time frame: From the start of the treatment until the criteria for progression are met, up to 5 years
Overall response rate for irradiated lesions (ORR)
Estimate the overall response rate (ORR) for unirradiated lesions for nivolumab/ipilimumab/radiation in metastatic, microsatellite stable colorectal cancer by RECIST 1.1. ORR is the number of patients that achieve either a CR or PR. * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. * Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
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Time frame: From the start of the treatment until disease progression/recurrence, up to 5 years
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE 5
Toxicity rates associated with the protocol treatment of nivolumab and ipilimumab combined with radiation will be summarized by category and grade.
Time frame: 6 Weeks
Progression-free survival (PFS)
Duration from the first day of protocol treatment to the earliest date of tumor progression by RECIST or clinical criteria, appearance of new metastases, or death due to any cause.
Time frame: Duration from the first day of protocol treatment to the earliest date of tumor progression by RECIST or clinical criteria, appearance of new metastases, or death due to any cause, up to 5 years
Overall survival (OS)
Duration from the first day of protocol treatment to the date of death due to any cause. Patients will be censored at the date of last follow-up.
Time frame: Duration from the first day of protocol treatment to the date of death due to any cause, up to 5 years