Infliximab or Vedolizumab in Treating Immune Checkpoint Inhibitor-Related Colitis in Patients With Genitourinary Cancer or Melanoma

Overview

This phase I/II trial studies the side effects of infliximab and vedolizumab and to see how well they work in treating inflammation of the colon (colitis) caused by immune checkpoint inhibitor therapy in patients with cancer of the genital and urinary organs (genitourinary) or melanoma. Monoclonal antibodies, such as infliximab or vedolizumab, may help to treat immunotherapy induced colitis/diarrhea. This study may help to identify the optimal treatment strategy for immune checkpoint inhibitor-related colitis in patients with genitourinary cancer or melanoma.

Full Title of Study: “Treatment of Immune Checkpoint Inhibitor-Related Colitis With Infliximab or Vedolizumab: A Randomized Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 31, 2021

Detailed Description

PRIMARY OBJECTIVES:

I. To compare the efficacy of infliximab and vedolizumab for clinical remission/response of immune-related diarrhea/colitis (immune-mediated colitis [IMC]).

II. To assess the safety and tolerability of IMC treatment.

SECONDARY OBJECTIVES:

I. To assess the efficacy of infliximab and vedolizumab for clinical remission/response of IMC at 4 weeks.

II. To assess the success of corticosteroid tapering. III. To measure the recurrence rate after corticosteroid taper.

EXPLORATORY OBJECTIVES:

I. To assess the efficacy of infliximab and vedolizumab to achieve endoscopic remission of immune-related diarrhea/colitis.

II. To assess the efficacy of infliximab and vedolizumab to achieve histological remission of immune-related diarrhea/colitis.

III. To assess the time duration to achieve the clinical remission/response. IV. To assess the long term outcome of cancer. V. To assess immunological, molecular and microbiome changes in tissue/blood/stool.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive infliximab intravenously (IV) over 1 hour once at week 0, 2, 6 for a total of 3 doses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive vedolizumab IV over 1 hour once at week 0, 2, 6 for a total of 3 doses in the absence of disease progression or unacceptable toxicity.

Patients are followed up weekly for 1 month and then at 2 and 3 months after the treatment.

Interventions

  • Biological: Infliximab
    • Given IV
  • Biological: Vedolizumab
    • Given IV

Arms, Groups and Cohorts

  • Active Comparator: Arm I (infliximab)
    • Patients receive infliximab IV over 1 hour once at week 0, 2, 6 for a total of 3 doses in the absence of disease progression or unacceptable toxicity.
  • Experimental: Arm II (vedolizumab)
    • Patients receive vedolizumab IV over 1 hour at week 0, 2, 6 for a total of 3 doses in the absence of disease progression or unacceptable toxicity.

Clinical Trial Outcome Measures

Primary Measures

  • Clinical remission/response rate of immune-mediated colitis (IMC)
    • Time Frame: At 2 weeks after initiation of infliximab or vedolizumab with corticosteroid taper
    • The difference of the remission rate between standard of care (infliximab + corticosteroid) and the treatment with vedolizumab + corticosteroid will be calculated along with the 95% confidence interval.
  • Treatment-related adverse events
    • Time Frame: Within 3 months after initiation of infliximab or vedolizumab
    • Will follow standard reporting guidelines for adverse events. Safety data will be summarized by category, severity and frequency.

Secondary Measures

  • Clinical remission/response rate of IMC
    • Time Frame: At 4 weeks after initiation of infliximab or vedolizumab with corticosteroid taper
    • Will be estimated and compared between the two treatment arms using chi-square test.
  • Complete weaning of corticosteroid
    • Time Frame: Within 4 weeks after infliximab or vedolizumab initiation without rebound of IMC
    • Will be estimated and compared between the two treatment arms using chi-square test.
  • Recurrent immune-related diarrhea/colitis
    • Time Frame: Within 3 months after corticosteroid taper
    • Will be estimated and compared between the two treatment arms using chi-square test.

Participating in This Clinical Trial

Inclusion Criteria

  • Patients who receive any type of immune checkpoint inhibitor (ICI) therapy
  • Patients with IMC of grade >= 2 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
  • Patients with ability to understand and willingness to sign informed consent
  • Patients with genitourinary cancer or melanoma or non-small cell lung cancer

Exclusion Criteria

  • Patients with positive infection at gastrointestinal symptoms onset
  • Patients are on concurrent immunosuppressive therapies other than what will be given for colitis
  • Patients with preexisting active inflammatory bowel disease or radiation enterocolitis
  • Pregnant and breastfeeding women, and women of child-bearing potential who have positive urine or serum pregnancy test or refuse to do pregnancy test

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • M.D. Anderson Cancer Center
  • Collaborator
    • National Cancer Institute (NCI)
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Yinghong Wang, Principal Investigator, M.D. Anderson Cancer Center
  • Overall Contact(s)
    • Yinghong Wang, 713-792-7672, ywang59@mdanderson.org

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