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

Treatment of Immune Checkpoint Inhibitor-Related Colitis With Infliximab or Vedolizumab: A Randomized Trial

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Malignant Solid Neoplasm; Melanoma; Colitis; Lung Non-Small Cell Carcinoma; Malignant Genitourinary System Neoplasm
• Intervention / Treatment: Biological: Infliximab; Biological: Vedolizumab

Detailed Description

PRIMARY OBJECTIVES:

I. To compare the efficacy of infliximab and vedolizumab for clinical remission/response of immune-related diarrhea and/or colitis.

II. To assess the safety and tolerability of the treatment for immune-mediated diarrhea and/or colitis.

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 and/or colitis.

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

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients who receive any type of immune checkpoint inhibitor (ICI) therapy
• Patients with peak grade >= 2 immune-related diarrhea and/or colitis (according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 within 45 days prior to initiation of study treatment (infliximab/ vedolizumab)
• Patients with ability to understand and willingness to sign informed consent
• Patients with genitourinary cancer or melanoma or non-small cell lung cancer
• No concern for active concomitant GI infection for immune-related diarrhea and/or colitis work up at the time of protocol therapy initiation as confirmed by stool tests or as per the treating physician based on clinical presentation
• Patient who has been cleared for enrollment by Infectious Diseases consultant or treating physician if positive infection workup or screening tests (e.g. lifelong positive T-spot due to BCG inoculation, chronic colonization) prior to initiation of diarrhea/colitis treatment

Exclusion Criteria:

• Patients younger than 18 years of age
• Patients with persistent gastrointestinal infection confirmed with positive testing despite completing 5 days of antibiotics
• Patients are on concurrent immunosuppressive therapies other than what will be given for colitis
• Patients with preexisting activehistory of inflammatory bowel disease and/or radiation enterocolitis with active disease status at the time of study treatment initiation
• Pregnant and breastfeeding women, and
• Women of child-bearing potential who have positive urine or serum pregnancy test or refuse to do pregnancy test unless last menstrual cycle was > 1 year prior to consent and/ or clear documentation states that patient is peri- or post-menopausal or there was recent supporting objective evidence of 'no pregnancy' status (e.g. blood or imaging) within 30 days prior to initiation of study treatment
• Patients who develop concurrent non-GI toxicity at the time of study treatment initiation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Biological: Infliximab; Given IV; Other Names: Remicade; Remsima; Avakine; cA2
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.	Biological: Vedolizumab; Given IV; Other Names: Entyvio; MLN0002; MLN02; LDP-02; Immunoglobulin G1, anti-(human integrin LPAM-1 (lymphocyte Peyer''s patch adhesion molecule 1)) (human-Mus musculus heavy chain), disulfide with human-Mus musculus kappa-chain, dimer; LDP 02; LDP02

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical remission/response rate of immune-mediated colitis (IMC)	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.	At 2 weeks after initiation of infliximab or vedolizumab with corticosteroid taper
Treatment-related adverse events	Will follow standard reporting guidelines for adverse events. Safety data will be summarized by category, severity and frequency.	Within 3 months after initiation of infliximab or vedolizumab

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endoscopic remission (Mayo Clinic sub-score 0-1) of immune-related diarrhea/colitis	Will be compared between the two treatment arms.	At 4 and 8 weeks after initiation of infliximab or vedolizumab treatment
Histological remission (resolution of active inflammation) of immune-related diarrhea/colitis	Will be compared between the two treatment arms.	At 8 weeks after initiation of infliximab or vedolizumab treatment
Time duration to achieve clinical remission/response	Will be estimated using the method of Kaplan and Meier. Comparisons of the time-to-event endpoint by important subgroups will be made using the log-rank tests.	From initiation of infliximab or vedolizumab treatment to clinical remission/response or last follow-up, assessed up to 3 months
Overall survival	Will be estimated using the method of Kaplan and Meier.	From the initiation of infliximab or vedolizumab treatment till death or last follow-up, assessed up to 3 months
Change in levels of cytokines in tissue/blood/stool samples	Will be compared using 2-sample t-test.	Baseline up to 3 months after infliximab or vedolizumab treatment
Change in frequencies of immune cells in tissue/blood/stool samples	Will be compared using 2-sample t-test.	Baseline up to 3 months after infliximab or vedolizumab treatment

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Yinghong Wang, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2020
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 27, 2020
• First Submitted That Met QC Criteria: May 27, 2020
• First Posted (Actual): May 29, 2020

Study Record Updates

• Last Update Posted (Estimated): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Intestinal Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Digestive System Diseases; Gastrointestinal Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Lung Neoplasms; Skin Diseases; Gastroenteritis; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Colitis; Carcinoma, Non-Small-Cell Lung; Melanoma; Urogenital Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Sulfur Compounds; Organic Chemicals; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Inorganic Chemicals; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Hydrogen Sulfide; Infliximab; Immunoglobulin G; vedolizumab; Disulfides; CT-P13; LDP-02
• Other Study ID Numbers: 2019-0276 (Other Identifier: M D Anderson Cancer Center); NCI-2019-04986 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No