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

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.

Inclusion criteria

• 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
• Treatment with any ICPI agent(s)
• 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
• 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
• 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)
• 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 and/ or imaging (e.g. CXR, CT CAP etc) confirms the absence of active infections (e.g. TB) within 60 days 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
• Participants 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 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
• 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.
• Participants who develop concurrent non-GI toxicity at the time of study treatment
• Donors at risk for monkeypox infection and/ or exposure as determined by a questionnaire