Nivolumab and Ipilimumab in Mucinous Colorectal and Appendiceal Tumors
Condition: Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum
MeSH terms: Adenocarcinoma; Adenocarcinoma, Mucinous; Cystadenocarcinoma; Appendiceal Neoplasms
Intervention: Nivolumab; Ipilimumab
Intervention description: IV infusion per institutional guidelines and the Package Insert; IV infusion per institutional guidelines and the Package Insert
Intervention MeSH terms: Nivolumab; Ipilimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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 < 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