Nivolumab and Ipilimumab in Mucinous Colorectal and Appendiceal Tumors
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Nivolumab and Ipilimumab Treatment will consist of nivolumab 480mg every 4 weeks and ipilimumab 1mg/kg every 8 weeks. |
Drug: Nivolumab
IV infusion per institutional guidelines and the Package Insert
Drug: Ipilimumab
IV infusion per institutional guidelines and the Package Insert
|
Outcome Measures
Primary Outcome Measures
- Six-month progression-free survival [6 months]
To determine six-month progression-free survival by iRECIST
Eligibility Criteria
Criteria
Inclusion Criteria:
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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.
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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.
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Microsatellite stable by PCR and/or mismatch repair proficient by immunohistochemistry
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ECOG performance status of 0 or 1
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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
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Measurable disease by RECIST v. 1.1
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Laboratory parameters:
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Absolute neutrophil count > 1500/μL
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Platelets > 100,000/μL
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Hemoglobin > 9.0 g/dL
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PT/INR or PTT < 1.5xULN
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Creatinine < 1.5xULN OR creatinine clearance > 50 mL/min by Cockcroft-Gault formula
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Total bilirubin < 1.5xULN
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Subjects with Gilbert's Syndrome must have a total bilirubin level of < 3.0xULN
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Albumin > 3.0 g/dL
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AST and/or ALT: < 3.0×ULN
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Subjects with HIV are permitted provided they meet the following criteria:
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CD4+ cell count > 250 cells/mm3
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No history of AIDS-defining conditions other than low CD4+ count
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If subject is on antiretroviral therapy, there must not be expected significant drug-drug interactions with study treatment
Exclusion Criteria:
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Bowel obstruction within the past 60 days
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Subjects who are currently pregnant, planning to become pregnant, or breast-feeding.
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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
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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
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Subjects who, in the opinion of the physician, would not be clinically appropriate for receipt of the therapy regimen associated with participation
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Subjects with contraindications to immune checkpoint therapy, as follows:
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Interstitial lung disease that is symptomatic or may interfere with the detection and management of suspected drug-related pulmonary toxicity
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Prior organ allograft or allogeneic bone marrow transplantation
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Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
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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
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Condition requiring systemic treatment with corticosteroids
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Systemic steroids at physiologic doses (equivalent to dose of oral prednisone 10 mg) are permitted.
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Intranasal, inhaled, topical, intra-articular, and ocular corticosteroids with minimal systemic absorption are permitted.
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Established non-peritoneal metastatic disease, including but not limited to metastases to the liver, lung, brain, extra-abdominal lymph nodes, and bone
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A second primary malignancy that, in the judgment of the investigator, may affect interpretation of results
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Prior treatment with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody
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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:
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No chemotherapy within 14 days prior to first dose
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No investigational product(s) (IPs) and/or biologic therapy within 28 days or 5 half-lives, whichever is longer, prior to first dose
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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.
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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.
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Active hepatitis B or hepatitis C, defined as the following:
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Hepatitis B surface antigen positive or HBV DNA PCR >100 IU/mL
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Hepatitis C antibody positive unless HCV RNA PCR is negative (i.e. undetectable viral load)
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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.)
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Participants who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Abramson Cancer Center of the University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
Sponsors and Collaborators
- Abramson Cancer Center of the University of Pennsylvania
Investigators
- Principal Investigator: Peter O'Dwyer, MD, Abramson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- UPCC 28218