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

Official title

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

Overview

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.

Interventions

• Procedure Fecal Microbiota Transplantation
  Undergo FMT via colonoscopy
• Drug Loperamide
  Given PO

Primary outcome measures

• Incidence of fecal microbiota transplantation (FMT)-related adverse events [Time frame: Up to 3 months post-FMT]
• Clinical response/remission of immune-related diarrhea/colitis [Time frame: At 2 weeks post-FMT]

Secondary outcome measures (1)

• Recurrent immune-related diarrhea/colitis within 3 months post-FMT after initially achieving clinical remission/response [Time frame: Up to 3 months post-FMT]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• M D Anderson Cancer Center — Houston

Identifiers

NCT: NCT04038619 · 2018-0663 · NCI-2019-02660 · 2018-0663

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗