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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04038619
• Other study ID #: 2018-0663
• Secondary ID: NCI-2019-0266020
• Status: Recruiting
• Phase: Phase 1
• Start date: February 1, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2024
• Source: M.D. Anderson Cancer Center
• Contact: Yinghong Wang
• Phone: 281-221-9138
• Email: ywang59[@]mdanderson.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Cervical Cancer
• Colitis
• Diarrhea
• Lung Cancer
• Malignant Genitourinary System Neoplasm
• Melanoma
• Ovarian Cancer
• Urogenital Neoplasms
• Uterine Cancer
• Uterine Neoplasms

Intervention

Procedure:
• Fecal Microbiota Transplantation
Undergo FMT via colonoscopy

Drug:
• Loperamide
Given PO

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Endoscopic remission (Mayo Clinic sub-score 0-1) of immune-related diarrhea/colitis	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).	At 4 weeks and 8 weeks post-FMT
Other	Histological remission (resolution of active inflammation) of immune-related diarrhea/colitis	Histological remission is defined resolution of active inflammation on biopsy sample.	At 8 weeks post-FMT
Other	Recurrent immune-related diarrhea/colitis following FMT and immune checkpoint inhibitors (ICPI) resumption within 6 months of ICPI resumption	Recurrent immune-related diarrhea colitis events occurring post-FMT will be recorded throughout the follow-up period.	Up to 6 months after restarting ICPI
Other	Measure immunological measures (including levels of cytokines (IL-6, 17, TNF, etc.) in tissue/blood/stool samples	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.	Up to 3 months
Other	Frequencies of immune cells (CD4/8 T cells, regulatory T cells [Treg], macrophages, etc.) in tissue/blood/stool samples	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.	Up to 3 months
Primary	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
Primary	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	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

External Links

•   MD Anderson Cancer Center