Nivolumab and Ipilimumab in Treating Patients with Mucinous Colorectal or Appendix Cancer Metastatic to the Peritoneum

Inclusion Criteria

• Subjects must have signed and dated an Institutional Review Board (IRB)-approved written informed consent form prior to the performance of any protocol-related procedures that are not part of standard care.
• Colorectal or appendiceal mucinous adenocarcinoma with peritoneal-only metastatic disease. It is recognized that in some patients, peritoneal disease will predominate without distinction of the site of origin, and such patients will be eligible.
• Microsatellite stable by polymerase chain reaction (PCR) and/or mismatch repair proficient by immunohistochemistry.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Prior therapy with a fluoropyrimidine, oxaliplatin, and irinotecan unless contraindicated or refused. Prior treatment with antiangiogenic and/or anti-EGFR antibody therapy is permitted but not required.
• Measurable disease by RECIST v. 1.1.
• Absolute neutrophil count >= 1500/uL.
• Platelets >= 100,000/uL.
• Hemoglobin >= 9.0 g/dL.
• Prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) =< 1.5 x upper limit of normal (ULN).
• Creatinine =< 1.5 x ULN OR creatinine clearance >= 50 mL/min by Cockcroft-Gault formula.
• Total bilirubin =< 1.5 x ULN. * Subjects with Gilbert’s syndrome must have a total bilirubin level of =< 3.0 x ULN.
• Albumin >= 3.0 g/dL.
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT): =< 3.0 x ULN.
• Subjects with human immunodeficiency virus (HIV) are permitted provided they meet the following criteria: * CD4+ cell count >= 250 cells/mm^3. * No history of acquired immunodeficiency syndrome (AIDS)-defining conditions other than low CD4+ count. * If subject is on antiretroviral therapy, there must not be expected significant drug-drug interactions with study treatment.

Exclusion Criteria

• Bowel obstruction within the past 60 days.
• Subjects who are currently pregnant, planning to become pregnant, or breast-feeding. * Females participants of child-bearing potential are required to use an effective contraception method or abstain from intercourse during treatment and for at least 5 months following the last dose. * Males participants with partners of child-bearing potential are required to use an effective contraception method or abstain from intercourse during treatment and for at least 7 months following the last dose.
• Subjects who, in the opinion of the physician, would not be clinically appropriate for receipt of the therapy regimen associated with participation.
• Subjects with contraindications to immune checkpoint therapy, as follows: * Interstitial lung disease that is symptomatic or may interfere with the detection and management of suspected drug-related pulmonary toxicity. * Prior organ allograft or allogeneic bone marrow transplantation. * Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication * Active autoimmune disease, except for vitiligo, type 1 diabetes mellitus, asthma, atopic dermatitis, or endocrinopathies manageable by hormone replacement; other autoimmune conditions may be allowable at the discretion of the principal investigator. * Condition requiring systemic treatment with corticosteroids. ** Systemic steroids at physiologic doses (equivalent to dose of oral prednisone 10 mg) are permitted. ** Intranasal, inhaled, topical, intra-articular, and ocular corticosteroids with minimal systemic absorption are permitted.
• Established non-peritoneal metastatic disease, including but not limited to metastases to the liver, lung, brain, extra-abdominal lymph nodes, and bone.
• A second primary malignancy that, in the judgment of the investigator, may affect interpretation of results.
• Prior treatment with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody.
• Toxicities attributed to prior anti-cancer therapy other than alopecia, fatigue, and peripheral neuropathy must have resolved to grade 1 or baseline before administration of study drug. In addition, a washout period will be required for prior therapies as specified: * No chemotherapy within 14 days prior to first dose. * No investigational product(s) (IPs) and/or biologic therapy within 28 days or 5 half-lives, whichever is longer, prior to first dose. * No major surgery within 28 days prior to first dose. Any surgery-related adverse events (AE)(s) must have resolved at least 14 days prior to first dose. * No radiation therapy with curative intent within 28 days prior to first dose. Prior focal palliative radiotherapy must have been completed at least 14 days prior to first dose.
• Active hepatitis B or hepatitis C, defined as the following: * Hepatitis B surface antigen positive or hepatitis B virus (HBV) DNA PCR > 100 IU/mL. * Hepatitis C antibody positive unless hepatitis C virus (HCV) ribonucleic acid (RNA) PCR is negative (i.e. undetectable viral load).
• Prisoners or participants who are involuntarily incarcerated. (Note: under specific circumstances a person who has been imprisoned may be included as a participant. Strict conditions apply and Bristol-Myers Squibb [BMS] approval is required.)
• Participants who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.