- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04407247
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
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Yinghong Wang
- Phone Number: 713-792-7672
- Email: ywang59@mdanderson.org
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- Recruiting
- M D Anderson Cancer Center
-
Principal Investigator:
- Yinghong Wang
-
Contact:
- Yinghong Wang
- Phone Number: 713-792-7672
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
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)
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.
|
Given IV
Other Names:
|
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.
|
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
At 2 weeks after initiation of infliximab or vedolizumab with corticosteroid taper
|
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.
|
Within 3 months after initiation of infliximab or vedolizumab
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
At 4 weeks after initiation of infliximab or vedolizumab with corticosteroid taper
|
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.
|
Within 4 weeks after infliximab or vedolizumab initiation without rebound of IMC
|
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.
|
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
Time Frame: At 4 and 8 weeks after initiation of infliximab or vedolizumab treatment
|
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
Time Frame: At 8 weeks after initiation of infliximab or vedolizumab treatment
|
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
Time Frame: From initiation of infliximab or vedolizumab treatment to clinical remission/response or last follow-up, assessed up to 3 months
|
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
Time Frame: From the initiation of infliximab or vedolizumab treatment till death or last follow-up, assessed up to 3 months
|
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
Time Frame: Baseline up to 3 months after infliximab or vedolizumab treatment
|
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
Time Frame: Baseline up to 3 months after infliximab or vedolizumab treatment
|
Will be compared using 2-sample t-test.
|
Baseline up to 3 months after infliximab or vedolizumab treatment
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Yinghong Wang, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Respiratory Tract Diseases
- Neoplasms by Histologic Type
- Lung Diseases
- Neoplasms by Site
- Gastrointestinal Diseases
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Gastroenteritis
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Colonic Diseases
- Intestinal Diseases
- Lung Neoplasms
- Neuroendocrine Tumors
- Nevi and Melanomas
- Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Melanoma
- Colitis
- Physiological Effects of Drugs
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Immunologic Factors
- Gastrointestinal Agents
- Dermatologic Agents
- Tumor Necrosis Factor Inhibitors
- Immunoglobulins
- Vedolizumab
- Infliximab
- Immunoglobulin G
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
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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