Nivolumab and Ipilimumab and Radiation Therapy in Metastatic, Microsatellite Stable Colorectal Cancer
Overview
- Phase
- Phase 2
- Intervention
- Nivolumab
- Conditions
- Metastatic Microsatellite Stable Colorectal Cancer
- Sponsor
- Massachusetts General Hospital
- Enrollment
- 32
- Locations
- 3
- Primary Endpoint
- Overall response rate for unirradiated lesions (ORR)
- Status
- Active, not recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
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
Detailed Description
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.
Investigators
Theodore Sunki Hong
Principal Investigator
Massachusetts General Hospital
Eligibility Criteria
Inclusion Criteria
- •Participants must have histologically or cytologically confirmed adenocarcinoma of colorectal origin
- •Age \>18 years.
- •ECOG performance status \<1
- •Life expectancy of greater than 3 months
- •Participants must have normal organ and marrow function as defined in Table 1, all screening labs should be performed within 14 days of protocol registration.
- •Table 1 Adequate Organ Function Laboratory Values:
- •System Laboratory Value
- •Hematological
- •Absolute neutrophil count (ANC) ≥1000 /mcL
- •White blood count (WBC) ≥2000 /mcL
Exclusion Criteria
- •Participants who have had chemotherapy, targeted small molecule therapy or study therapy within 14 days of protocol treatment, or those who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 2 weeks earlier. Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- •Patients who have had radiation within 8 weeks prior to protocol registration.
- •Participants who are receiving any other investigational agents.
- •Patients are excluded if they have an active, known or suspected autoimmune disease other than those listed below. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
- •Patients are excluded if they have a condition requiring systemic treatment with either corticosteroids (\> 12 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 12 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Subjects are permitted to use topical, ocular, intraarticular, intranasal, and inhalational corticosteroids (with minimal systemic absorption).
- •Physiologic replacement doses of systemic corticosteroids are permitted, even if \> 12 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
- •Patients are excluded if they have previously received anti-CTLA-4 therapy. Prior anti- PD-1 or anti-PD-L1 therapy is permitted with 6-month washout period unless the following treatment-related toxicities are present:
- •Any toxicity NCI CTCAE grade \>/= 3 from previous immunotherapy that did not resolve to grade 1 with or without immunosuppressive therapy. Patients must be off all immunosuppressive therapy prior to enrollment.
- •Myocarditis, any grade.
- •Pneumonitis, any grade.
Arms & Interventions
Nivolumab+Ipilimumab+Radiation Therapy (RT)
Study cycles are 6 weeks long, participants will receive: Cycle 1: Nivolumab every 2 weeks during cycle, Ipilimumab 1x on Day 1 of cycle, and Radiation Therapy every other weekday or 2 days for a total of 3 treatments during week 1 of Cycle 1 only. Cycles 2-4: Nivolumab every 2 weeks during each cycle, Ipilimumab 1x on Day 1 of each cycle Cycles 5-Disease Progression: Nivolumab every 2 weeks during each cycle
Intervention: Nivolumab
Nivolumab+Ipilimumab+Radiation Therapy (RT)
Study cycles are 6 weeks long, participants will receive: Cycle 1: Nivolumab every 2 weeks during cycle, Ipilimumab 1x on Day 1 of cycle, and Radiation Therapy every other weekday or 2 days for a total of 3 treatments during week 1 of Cycle 1 only. Cycles 2-4: Nivolumab every 2 weeks during each cycle, Ipilimumab 1x on Day 1 of each cycle Cycles 5-Disease Progression: Nivolumab every 2 weeks during each cycle
Intervention: Ipilimumab
Nivolumab+Ipilimumab+Radiation Therapy (RT)
Study cycles are 6 weeks long, participants will receive: Cycle 1: Nivolumab every 2 weeks during cycle, Ipilimumab 1x on Day 1 of cycle, and Radiation Therapy every other weekday or 2 days for a total of 3 treatments during week 1 of Cycle 1 only. Cycles 2-4: Nivolumab every 2 weeks during each cycle, Ipilimumab 1x on Day 1 of each cycle Cycles 5-Disease Progression: Nivolumab every 2 weeks during each cycle
Intervention: Radiation Therapy
Outcomes
Primary Outcomes
Overall response rate for unirradiated lesions (ORR)
Time Frame: From the start of the treatment until disease progression/recurrence, up to 5 years
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.
Secondary Outcomes
- Disease control rate (DCR)(From the start of the treatment until the criteria for progression are met, up to 5 years)
- Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE 5(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, up to 5 years)
- Overall survival (OS)(Duration from the first day of protocol treatment to the date of death due to any cause, up to 5 years)
- Overall response rate for irradiated lesions (ORR)(From the start of the treatment until disease progression/recurrence, up to 5 years)