Nivolumab and Ipilimumab and Radiation Therapy in MSS and MSI High Colorectal and Pancreatic Cancer

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Disease Information

Descriptive Information
Brief Title † Nivolumab and Ipilimumab and Radiation Therapy in MSS and MSI High Colorectal and Pancreatic Cancer
Official Title † Nivolumab and Ipilimumab and Radiation Therapy in Microsatellite Stable (MSS) and Microsatellite Instability (MSI) High Colorectal and Pancreatic Cancer
Brief Summary This research study is studying a combination of drugs with radiation therapy as a possible treatment for Microsatellite Stable Colorectal Cancer, Pancreatic Cancer, or MSI High Colorectal Cancer. The interventions involved in this study are: - Nivolumab - Ipilimumab - 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 FDA (the U.S. Food and Drug Administration) has not approved nivolumab for this specific disease but it has been approved for other uses. The FDA (the U.S. Food and Drug Administration) has not approved ipilimumab for this specific disease but it has been approved for other uses. Researchers hope to study the effects of the combination of Nivolumab and Ipilimumab. Many cancers use specific pathways (such as PD-1/PD-L1 and CTLA-4) to evade the body's immune system. Nivolumab and ipilimumab work by blocking the PD-1/PD-L1 and CTLA-4 pathways and thus releasing the brakes on the immune system so it can stop or slow cancer. Ipilimumab and Nivolumab are both antibodies. An antibody is a cell that attaches to other cells to fight off infection. The antibodies in ipilimumab work by not allowing cancer cell growth. The antibodies in nivolumab work by causing programmed cell death of the cancer cells. Radiation therapy is believed to increase the likelihood of response of immunotherapy (the prevention/treatment of a disease through an immune response). In this research study, the investigators are studying the combination of nivolumab, ipilimumab and radiation therapy on participants with microsatellite stable colorectal cancer, pancreatic cancer, or MSI high colorectal cancer. The combination of these study drugs have been tested and optimized for safety and is currently being tested in multiple disease types. The study drugs have not been tested and optimized in combination with radiation therapy. The investigators believe that through the combination of the study drugs and radiation therapy the body may produce an immune response to stop the cancer cells from growing.
Study Phase Phase 2
Study Type † Interventional
Study Design †
Primary Outcome Measure † Disease Control Rate
Secondary Outcome Measure † Median Progression free Survival
Condition † Microsatellite Stable Colorectal Cancer Pancreatic Cancer MSI High Colorectal Cancer
Intervention † DrugNivolumab
Study Arms / Comparison Groups Nivolumab+Ipilimumab Nivolumab will be administered intravenously 3 times per cycle Ipilimumab will be administered intravenously once per cycle Radiation Therapy will be administered per hospital standard
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Drug
Estimated Enrollment † 80
Start Date † May 10, 2017
Completion Date October 31, 2024
Primary Completion Date October 31, 2020
Eligibility Criteria † Inclusion Criteria: - Participants must have histologically or cytologically confirmed adenocarcinoma of colorectal or pancreatic origin - Age >18 years. - Eastern Cooperative Oncology Group (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) ≥1500 /mcL - White blood count (WBC) ≥2000 /mcL - Platelets ≥100,000 / mcL - Hemoglobin ≥9 g/dL - Renal - Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤ Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below): - Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL - Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL - Hepatic - Serum total bilirubin ≤ 1.5 X ULN (upper limit of normal) (subjects with Gilbert Syndrome can have a total bilirubin 1 cm in size outside the radiation field that can be used as measurable disease - Colorectal patients must have documentation of microsatellite status. Immunohistochemistry (IHC) is acceptable. - Colorectal patients must have received prior Fluorouracil (5FU), Irinotecan and Oxaliplatin (any combination) or have a contraindication to receiving these agents. - Pancreas patients must have progressed on at least 1 prior line of chemotherapy 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. - 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 (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if > 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted. - Colorectal patients are excluded if they have had prior systemic treatment with an anti-CTLA4, anti-PD1 (Programmed cell death protein 1) or PDL1 (Programmed death-ligand 1) antibody. Pancreatic patients are excluded if they have previously received anti-CTLA-4 therapy. Prior PD-1 or PDL1 therapy will be permitted for pancreas patients - Has a known history of active TB (Bacillus Tuberculosis) - Patients are excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection - Patients are excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). These participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated. - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. - Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. - Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 5 months for woman and 7 months for men, after the last dose of trial treatment. - Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. - Has known history of, or any evidence of active, non-infectious pneumonitis. - Has an active infection requiring systemic therapy. - Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed. - History of allergy to study drug components - History of severe hypersensitivity reaction to any monoclonal antibody - Uncontrolled brain metastases. Patients treated with radiation > 4 weeks prior with follow up imaging showing control are eligible
Gender All
Ages 18 Years - N/A
Accepts Healthy Volunteers No
Contacts †† Theodore Hong, 617-724-8770,
Location Countries † United States
Administrative Information
NCT ID † NCT03104439
Organization ID 17-021
Secondary IDs ††
Responsible Party Principal Investigator
Study Sponsor † Massachusetts General Hospital
Collaborators †† Bristol-Myers Squibb
Investigators † Principal Investigator: Theodore Hong, MD, Massachusetts General Hospital
Information Provided By
Verification Date May 2017
First Received Date † April 3, 2017
Last Updated Date May 29, 2017
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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