Clinical trial NCT04407247: Infliximab or Vedolizumab in Treating Immune Checkpoint Inhibitor-Related Colitis in Patients With Genitourinary Cancer or Melanoma
Official title: Treatment of Immune Checkpoint Inhibitor-Related Colitis With Infliximab or Vedolizumab: A Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Colitis
Lung Non-Small Cell Carcinoma
Malignant Genitourinary System Neoplasm
Malignant Solid Neoplasm
Melanoma
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2020-05-29
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical remission/response rate of immune-mediated colitis (IMC)
timeFrame: At 2 weeks after initiation of infliximab or vedolizumab with corticosteroid taper
measure: Treatment-related adverse events
timeFrame: Within 3 months after initiation of infliximab or vedolizumab
Secondary outcomes:
measure: Clinical remission/response rate of IMC
timeFrame: At 4 weeks after initiation of infliximab or vedolizumab with corticosteroid taper
measure: Complete weaning of corticosteroid
timeFrame: Within 4 weeks after infliximab or vedolizumab initiation without rebound of IMC
measure: Recurrent immune-related diarrhea/colitis
timeFrame: Within 3 months after corticosteroid taper
Other outcomes:
measure: Endoscopic remission (Mayo Clinic sub-score 0-1) of immune-related diarrhea/colitis
timeFrame: At 4 and 8 weeks after initiation of infliximab or vedolizumab treatment
measure: Histological remission (resolution of active inflammation) of immune-related diarrhea/colitis
timeFrame: At 8 weeks after initiation of infliximab or vedolizumab treatment
measure: Time duration to achieve clinical remission/response
timeFrame: From initiation of infliximab or vedolizumab treatment to clinical remission/response or last follow-up, assessed up to 3 months
measure: Overall survival
timeFrame: From the initiation of infliximab or vedolizumab treatment till death or last follow-up, assessed up to 3 months
measure: Change in levels of cytokines in tissue/blood/stool samples
timeFrame: Baseline up to 3 months after infliximab or vedolizumab treatment
measure: Change in frequencies of immune cells in tissue/blood/stool samples
timeFrame: Baseline up to 3 months after infliximab or vedolizumab treatment
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Yinghong Wang
role: PRINCIPAL_INVESTIGATOR
References: