Colitis, Lung Non-Small Cell Carcinoma, Malignant Genitourinary System Neoplasm, Malignant Solid Neoplasm, Melanoma
Conditions
Brief summary
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
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.
Interventions
BIOLOGICALInfliximab
Given IV
BIOLOGICALVedolizumab
Given IV
Sponsors
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical remission/response rate of immune-mediated colitis (IMC) | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Clinical remission/response rate of IMC | 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 | 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 | Within 3 months after corticosteroid taper | Will be estimated and compared between the two treatment arms using chi-square test. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORYinghong Wang
M.D. Anderson Cancer Center
Outcome results
None listed