Nivolumab and Ipilimumab in Mucinous Colorectal and Appendiceal Tumors

Sponsor:

Collaborators:

Information provided by (Responsible Party):

，

Tracking Information

First Submitted Date ^ICMJE

October 1, 2018

First Posted Date ^ICMJE

October 3, 2018

Last Update Posted Date

October 3, 2018

Actual Study Start Date ^ICMJE

November 2018

Estimated Primary Completion Date

November 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Six-month progression-free survival[ Time Frame: 6 months ]

To determine six-month progression-free survival by iRECIST

Original Primary Outcome Measures ^ICMJE

Same as current

Current Secondary Outcome Measures ^ICMJE

[ Time Frame: ]

Descriptive Information

Brief Title ^ICMJE

Nivolumab and Ipilimumab in Mucinous Colorectal and Appendiceal Tumors

Official Title ^ICMJE

A Phase II Study of Nivolumab and Ipilimumab in Mucinous Colorectal and Appendiceal Tumors

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.

Detailed Description

Study Type ^ICMJE

Interventional

Study Phase

Phase 2

Study Design ^ICMJE

Allocation:
Intervention Model: Single Group Assignment
Intervention Model Description:
Masking: Interventional
Masking Description:
Primary Purpose: Treatment

Condition ^ICMJE

Intervention ^ICMJE

Drug: Nivolumab
IV infusion per institutional guidelines and the Package Insert
Drug: Ipilimumab
IV infusion per institutional guidelines and the Package Insert

Study Arms

Experimental: Nivolumab and Ipilimumab
Treatment will consist of nivolumab 480mg every 4 weeks and ipilimumab 1mg/kg every 8 weeks.

Recruitment Information

Recruitment Status ^ICMJE

Not yet recruiting

Estimated Enrollment ^ICMJE

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date

November 2023

Estimated Primary Completion Date

November 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Sex/Gender

Sexes Eligible for Study:

All

Ages

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

Plan to Share IPD:

Responsible Party

，

Study Sponsor ^ICMJE

Abramson Cancer Center of the University of Pennsylvania

Collaborators ^ICMJE

Investigators ^ICMJE

Principal Investigator: Peter O'Dwyer, MD Abramson Cancer Center

PRS Account

Verification Date

October 2018

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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