Fecal Microbiota Transplantation in Treating Immune-Checkpoint Inhibitor Induced-Diarrhea or Colitis in Genitourinary Cancer Patients

Phase 1

Recruiting

• Conditions: Breast Cancer; Melanoma; Uterine Cancer; Colitis; Diarrhea; Ovarian Cancer; Cervical Cancer; Malignant Genitourinary System Neoplasm; Lung Cancer
• Interventions: Procedure: Fecal Microbiota Transplantation; Drug: Loperamide

• Registration Number: NCT04038619
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

This trial studies how well fecal microbiota transplantation works in treating diarrhea or colitis (inflammation of the intestines) that is caused by certain types of medications (called immune-checkpoint inhibitors) in patients with genitourinary cancer. Fecal microbiota transplantation may effectively reduce the incidence of immune checkpoint inhibitor-induced diarrhea/colitis.

Detailed Description

PRIMARY OBJECTIVES:

* To assess the safety and tolerability of fecal microbiota transplantation (FMT).

* To assess the efficacy of FMT for clinical remission/response of immune-related diarrhea/colitis.

SECONDARY OBJECTIVES:

- To measure the recurrence rate after achieving clinical remission/response of immune-related diarrhea/colitis.

EXPLORATORY OBJECTIVES:

* To assess the efficacy of FMT to achieve endoscopic remission of immune-related diarrhea/colitis.

* To assess the efficacy of FMT to achieve histological remission of immune-related diarrhea/colitis.

* To assess the efficacy of FMT on recurrence of immune-related diarrhea/colitis after resumption of immune checkpoint inhibitors (ICPI).

* To assess immunological, molecular and microbiome changes in tissue/blood/stool.

To study the efficacy and/ or benefit of PuraStat gel in the healing of mucosal ulcers and its hemostatic effect on bleeding lesions

OUTLINE:

Patients receive loperamide orally (PO). After 4 hours, patients undergo FMT via colonoscopy over 15-30 minutes.

After completion of study treatment, patients are followed up at 2, 4, and 8 weeks, and then at 3 months.

Study Timeline

• Study First Submitted: 2019-07-26
• Study First Submitted QC: 2019-07-26
• Study First Posted: 2019-07-31
• Study Start: 2021-02-01
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-30
• Last Update Posted: 2025-05-31
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Diagnosis of any type of genitourinary (kidney, bladder and prostate), melanoma, non-melanoma skin cancer, lung, head & neck, sarcoma/lymphoma, gastrointestinal system (luminal GI, hepatobiliary, pancreas), gynecology system (ovarian, uterine, cervical), and breast malignancies
2. Treatment with any ICPI agent(s)
3. Participants with new onset of ≥ grade 2 ICPI-induced diarrhea and/or colitis symptoms based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5 within 45 days prior to date of FMT treatment without involvement of non- GI toxicity
4. Participants with a history of steroid use before FMT can be allowed if last dose was > 30 days prior to FMT treatment or treatment duration was for <7 days beyond one week prior to FMT treatment
5. Participants with a history of immunosuppressant (Infliximab, Vedolizumab etc) use before FMT can be allowed if last dose was administered ≥ 3 months prior to FMT treatment when used for the treatment of conditions other than for ICI- induced GI toxicities (e.g., Infliximab is used in the treatment of Crohn's disease, rheumatoid arthritis, plaque psoriasis, and Vedolizumab is used in treating ulcerative colitis)
6. No concern for active concomitant GI infection at the time of initiation of protocol therapy as confirmed by stool tests or as per the treating physician based on clinical presentation
7. Participant 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 protocol therapy
8. Ability to understand and willingness to sign an informed consent form
9. Life expectancy > 6 months

Exclusion Criteria

1. Age younger than 18 years
2. Participants with persistent GI infection confirmed with positive stool test(s) despite completing 5 days of antibiotics prior to initiation of protocol therapy
3. History of inflammatory bowel disease, and/or radiation enteritis or colitis with active disease status at the time of study treatment initiation
4. Pregnant and breastfeeding women
5. Women 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 participant is peri- or post-menopausal or there has been recent supporting objective evidence of 'no pregnancy' status (e.g. blood or imaging) within 30 days prior to date of study treatment
6. Immunosuppressive treatment at onset of ICPI-induced diarrhea/colitis
7. Any medical conditions (e.g. severe heart failure, brain hemorrhage, septic shock, etc.) that are high risk for colonoscopy procedure by the assessment of the study PI or Co-PIs.
8. Participants who develop concurrent non-GI toxicity at the time of study treatment
9. Donors at risk for monkeypox infection and/ or exposure as determined by a questionnaire

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (loperamide, colonoscopy, FMT)	Fecal Microbiota Transplantation	Patients receive loperamide PO. After 4 hours, patients undergo FMT via colonoscopy over 15-30 minutes.
Treatment (loperamide, colonoscopy, FMT)	Loperamide	Patients receive loperamide PO. After 4 hours, patients undergo FMT via colonoscopy over 15-30 minutes.

Primary Outcome Measures

Name	Time	Method
Incidence of fecal microbiota transplantation (FMT)-related adverse events	Up to 3 months post-FMT	Assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5. All events are recorded with grade and attribution to FMT.
Clinical response/remission of immune-related diarrhea/colitis	At 2 weeks post-FMT	Clinical remission of immune related events defined as improvement of symptoms of grade 1 or lower within 2 weeks post-FMT. Clinical partial response of immune related diarrhea/colitis defined as improvement of diarrhea/colitis to a lower grade than the initial presentation but not meeting criteria of clinical remission at 2 week post-FMT time point.

Secondary Outcome Measures

Name	Time	Method
Recurrent immune-related diarrhea/colitis within 3 months post-FMT after initially achieving clinical remission/response	Up to 3 months post-FMT	Recurrent immune-related diarrhea colitis events occurring post-FMT are recorded throughout the follow-up period.

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States