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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Colitis, Lung Non-Small Cell Carcinoma, Malignant Genitourinary System Neoplasm, Malignant Solid Neoplasm, Melanoma

Intervention / Treatment
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* Biological: Infliximab
* Biological: Vedolizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I (infliximab)<br>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<br>* Given IV<br>* Other names: Remsima;|
| Experimental: Arm II (vedolizumab)<br>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<br>* Given IV<br>* Other names: MLN02;|

What is the study measuring?
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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 |