Nivolumab and Ipilimumab in Mucinous Colorectal and Appendiceal Tumors

Inclusion Criteria:

Subjects must have signed and dated an 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 PCR and/or mismatch repair proficient by immunohistochemistry
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

Laboratory parameters:

Absolute neutrophil count > 1500/μL
Platelets > 100,000/μL
Hemoglobin > 9.0 g/dL
PT/INR or PTT < 1.5xULN
Creatinine < 1.5xULN OR creatinine clearance > 50 mL/min by Cockcroft-Gault formula
Total bilirubin < 1.5xULN
Subjects with Gilbert's Syndrome must have a total bilirubin level of < 3.0xULN
Albumin > 3.0 g/dL
AST and/or ALT: < 3.0×ULN

Subjects with HIV are permitted provided they meet the following criteria:

CD4+ cell count > 250 cells/mm3
No history of 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 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 HBV DNA PCR >100 IU/mL
Hepatitis C antibody positive unless HCV 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 BMS approval is required.)
Participants who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness