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

Melanoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04407247
• Other study ID #: 2019-0276
• Secondary ID: NCI-2019-0498620
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 9, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2024
• Source: M.D. Anderson Cancer Center
• Contact: Yinghong Wang
• Phone: 713-792-7672
• Email: ywang59[@]mdanderson.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Biological:
• Infliximab
Given IV
• Vedolizumab
Given IV

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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

External Links

•   MD Anderson Cancer Center