Nivolumab and Ipilimumab in Mucinous Colorectal and Appendiceal Tumors

NCT03693846 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: UPCC 28218
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Progression-Free Survival at 6 Months

  To determine six-month progression-free survival by iRECIST from start of study treatment until 6 months

  Start of treatment until 6 months later

Secondary Outcomes (4)

• Progression-Free Survival

  start of treatment until disease progression or death, assessed up to 2 years

• Overall Survival

  From start of treatment until death assessed up to 2 years

• Objective Response Rate

  From start of treatment until progression or death assessed up to 2 years

• Duration of Response

  From the first recorded partial or complete response until progressive disease or death, whichever came first, assessed up to 2 years

Study Arms (1)

Nivolumab and Ipilimumab

EXPERIMENTAL

Treatment will consist of Nivolumab 480mg every 4 weeks and Ipilimumab 1mg/kg every 8 weeks. Subjects will continue on study therapy until disease progression, unacceptable toxicity, withdrawal of consent, or 24 months of therapy.

Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

IV infusion per institutional guidelines and the Package Insert

Also known as: Opdivo

Nivolumab and Ipilimumab

Ipilimumab DRUG

IV infusion per institutional guidelines and the Package Insert

Also known as: Yervoy

Nivolumab and Ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Interventions

Nivolumab; Ipilimumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Thomas Karasic, MD
• Organization: University of Pennsylvania

thomas.karasic@pennmedicine.upenn.edu

215-614-1858

Study Officials

• Thomas Karasic, MD

  Abramson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2018
• First Posted: October 3, 2018
• Study Start: February 15, 2019
• Primary Completion: March 6, 2021
• Study Completion: March 6, 2021
• Last Updated: October 20, 2022
• Results First Posted: October 20, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)