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

M.D. Anderson Cancer Center

Status and phase

Active, not recruiting

Phase 2

Phase 1

Conditions

Malignant Genitourinary System Neoplasm

Melanoma

Colitis

Malignant Solid Neoplasm

Lung Non-Small Cell Carcinoma

Treatments

Biological: Vedolizumab

Biological: Infliximab

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT04407247

2019-0276 (Other Identifier)

NCI-2019-04986 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

47 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

47 participants in 2 patient groups

Arm I (infliximab)

Active Comparator group

Description:

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.

Treatment:

Biological: Infliximab

Arm II (vedolizumab)

Experimental group

Description:

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.

Treatment:

Biological: Vedolizumab