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

Study Overview
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Brief Summary
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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
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PRIMARY OBJECTIVES: I. To assess the safety and tolerability of fecal microbiota transplantation (FMT). II. To assess the efficacy of FMT for clinical remission/response of immune-related diarrhea/colitis. SECONDARY OBJECTIVES: I. To measure the recurrence rate after achieving clinical remission/response of immune-related diarrhea/colitis. EXPLORATORY OBJECTIVES: I. To assess the efficacy of FMT to achieve endoscopic remission of immune-related diarrhea/colitis. II. To assess the efficacy of FMT to achieve histological remission of immune-related diarrhea/colitis. III. To assess the efficacy of FMT on recurrence of immune-related diarrhea/colitis after resumption of immune checkpoint inhibitors (ICPI). IV. To assess immunological, molecular and microbiome changes in tissue/blood/stool. 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.

Official Title
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Fecal Microbiota Transplantation (FMT) for Immune-Checkpoint Inhibitor Induced-Diarrhea/Colitis in Genitourinary Cancer Patients

Conditions
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Colitis, Diarrhea, Malignant Genitourinary System Neoplasm, Melanoma, Lung Cancer, Ovarian Cancer, Uterine Cancer, Breast Cancer, Cervical Cancer

Intervention / Treatment
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* Procedure: Fecal Microbiota Transplantation
* Drug: Loperamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of any type of genitourinary, melanoma, lung, ovarian, uterine, cervical, and breast malignancies Treatment with any ICPI agent(s) Patients 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 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 Patient 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 Ability to understand and willingness to sign an informed consent form Life expectancy > 6 months Exclusion Criteria Age younger than 18 years Patients with persistent GI infection confirmed with positive stool test(s) despite completing 5 days of antibiotics prior to initiation of protocol therapy History of inflammatory bowel disease, and/or radiation enteritis or colitis with active disease status at the time of study treatment initiation Pregnant and breastfeeding women 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 patient 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 Immunosuppressive treatment at onset of ICPI-induced diarrhea/colitis 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. Patients who develop concurrent non-GI toxicity at the time of study treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (loperamide, colonoscopy, FMT)<br>Patients receive loperamide PO. After 4 hours, patients undergo FMT via colonoscopy over 15-30 minutes. | Procedure: Fecal Microbiota Transplantation<br>* Undergo FMT via colonoscopy<br>* Other names: Stool Transplant;Drug: Loperamide<br>* Given PO<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of fecal microbiota transplantation (FMT)-related adverse events | Assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5. All events are recorded with grade and attribution to FMT. | Up to 3 months post-FMT | 
| Clinical response/remission of immune-related diarrhea/colitis | 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. | At 2 weeks post-FMT | 

Secondary Outcome Measures

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