Clinical trial NCT04038619: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Colitis
Diarrhea
Malignant Genitourinary System Neoplasm
Melanoma
Lung Cancer
Ovarian Cancer
Uterine Cancer
Breast Cancer
Cervical Cancer
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2019-07-31
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of fecal microbiota transplantation (FMT)-related adverse events
timeFrame: Up to 3 months post-FMT
measure: Clinical response/remission of immune-related diarrhea/colitis
timeFrame: At 2 weeks post-FMT
Secondary outcomes:
measure: Recurrent immune-related diarrhea/colitis within 3 months post-FMT after initially achieving clinical remission/response
timeFrame: Up to 3 months post-FMT
Other outcomes:
measure: Endoscopic remission (Mayo Clinic sub-score 0-1) of immune-related diarrhea/colitis
timeFrame: At 4 weeks and 8 weeks post-FMT
measure: Histological remission (resolution of active inflammation) of immune-related diarrhea/colitis
timeFrame: At 8 weeks post-FMT
measure: Recurrent immune-related diarrhea/colitis following FMT and immune checkpoint inhibitors (ICPI) resumption within 6 months of ICPI resumption
timeFrame: Up to 6 months after restarting ICPI
measure: Measure immunological measures (including levels of cytokines (IL-6, 17, TNF, etc.) in tissue/blood/stool samples
timeFrame: Up to 3 months
measure: Frequencies of immune cells (CD4/8 T cells, regulatory T cells [Treg], macrophages, etc.) in tissue/blood/stool samples
timeFrame: Up to 3 months
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Yinghong Wang
role: PRINCIPAL_INVESTIGATOR
References: