nivolumab and ipilimumab in mucinous colorectal and appendiceal tumors

Conditions: Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum

Summary: this is a single-arm phase ii study of twenty-one subjects with mucinous adenocarcinoma of the colon, rectum, or appendix with prior systemic therapy with a fluoropyrimidine, oxaliplatin, and irinotecan. treatment will consist of nivolumab 480mg every 4 weeks and ipilimumab 1mg/kg every 8 weeks until disease progression, unacceptable toxicity, or 2 years of therapy.

treatment will consist of nivolumab 480mg every 4 weeks and ipilimumab 1mg/kg every 8 weeks (within a 56-day cycle, (nivolumab administered on days 1 and 29, and ipilimumab administered on day 1 of each cycle). imaging assessments will be conducted every 8 weeks (+/-2 weeks) for the first 24 weeks then every 8-12 weeks (+/-2 weeks). if progression is noted on imaging in the setting of clinical stability, subjects may remain on study and have confirmatory imaging in 4-8 weeks per irecist criteria

Eligibility criteria:
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 \ 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