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

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04038619

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

5.9

Anticipated Duration (Months)

6.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Colitis Diarrhea Malignant Genitourinary System Neoplasm	Procedure: Fecal Microbiota Transplantation Drug: Loperamide	Phase 1

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.

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 Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 1, 2021

Anticipated Primary Completion Date :

Jul 31, 2021

Anticipated Study Completion Date :

Jul 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (loperamide, colonoscopy, FMT) Patients receive loperamide PO. After 4 hours, patients undergo FMT via colonoscopy over 15-30 minutes.	Procedure: Fecal Microbiota Transplantation Undergo FMT via colonoscopy Other Names: Fecal Material Transplantation Fecal Transplantation FMT Poo Transplant Poop Transplant Stool Transplant Drug: Loperamide Given PO

Arm

Intervention/Treatment

Experimental: Treatment (loperamide, colonoscopy, FMT)

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

Procedure: Fecal Microbiota Transplantation

Undergo FMT via colonoscopy

Other Names:

Fecal Material Transplantation

Fecal Transplantation

FMT

Poo Transplant

Poop Transplant

Stool Transplant

Drug: Loperamide

Given PO

Outcome Measures

Primary Outcome Measures

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

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.

Other Outcome Measures

Endoscopic remission (Mayo Clinic sub-score 0-1) of immune-related diarrhea/colitis [At 4 weeks and 8 weeks post-FMT]
Endoscopic remission is defined as Mayo Clinic endoscopic subscore 0 or 1 (absence of ulcers, with or without mild erythema, friability and decreased vascular pattern).
Histological remission (resolution of active inflammation) of immune-related diarrhea/colitis [At 8 weeks post-FMT]
Histological remission is defined resolution of active inflammation on biopsy sample.
Recurrent immune-related diarrhea/colitis following FMT and immune checkpoint inhibitors (ICPI) resumption within 6 months of ICPI resumption [Up to 6 months after restarting ICPI]
Recurrent immune-related diarrhea colitis events occurring post-FMT will be recorded throughout the follow-up period.
Measure immunological measures (including levels of cytokines (IL-6, 17, TNF, etc.) in tissue/blood/stool samples [Up to 3 months]
Blood, stool, and colon tissues will be collected from at each scheduled time point. Markers of interest for immunological and biological profiles include levels of cytokines (IL-6, 17, TNF, etc). Special attention will focus on Bacteroidetes, Akkermansia, and Blautia.
Frequencies of immune cells (CD4/8 T cells, regulatory T cells [Treg], macrophages, etc.) in tissue/blood/stool samples [Up to 3 months]
Blood, stool, and colon tissues will be collected from at each scheduled time point. Markers of interest for immunological and biological profiles include frequencies of immune cells (CD4/8 T cells, Treg, macrophages, etc). Special attention will focus on Bacteroidetes, Akkermansia, and Blautia.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of any type of genitourinary malignancy.
Treatment with any ICPI agent(s).
New onset of grade 2 or above ICPI-induced diarrhea/colitis.
Ability to understand and willingness to sign an informed consent form.
Life expectancy > 6 months.

Exclusion Criteria:

Diagnosed infection at the onset of ICPI- induced diarrhea/colitis requiring antibiotics.
History of inflammatory bowel disease, and/or radiation enteritis or colitis.
Pregnant and breastfeeding women.
Women who have positive urine or serum pregnancy test or refuse to do pregnancy test.
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 primary investigator (PI) or Co-PIs.