Stool Transplant for Immunotherapy-Related Diarrhea

Overseen By Robin Mendelsohn, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Corticosteroids, Biologics

Must not be taking: Antibiotics

Disqualifiers: Active GI infection, HIV, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a stool transplant, also known as Fecal Microbiota Transplantation (FMT), can help individuals with diarrhea caused by immune therapy for cancer. The treatment introduces healthy donor stool into the gut to improve gut health by adding beneficial bacteria. The trial targets individuals who continue to experience this type of diarrhea despite treatments like steroids or biologic drugs. Participants must have undergone immune therapy for cancer and have persistent diarrhea that impacts daily life. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken antibiotics within 48 hours before the stool transplant.

What prior data suggests that fecal microbiota transplantation (FMT) is safe for treating immunotherapy-related diarrhea?

Research has shown that Fecal Microbiota Transplantation (FMT) is generally safe. Studies have found that FMT can help treat conditions like colitis, an inflammation of the colon. Most recipients of FMT experience only mild side effects, such as temporary nausea, stomach pain, and diarrhea related to the treatment.

FMT has also been used for various health issues and is considered a practical option. It is usually well-tolerated by individuals undergoing different treatments, including cancer therapies. While some side effects can occur, they are typically not serious and tend to resolve on their own. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Most treatments for immunotherapy-related diarrhea involve medications that aim to control symptoms, like steroids or anti-inflammatory drugs. However, Fecal Microbiota Transplantation (FMT) is unique because it uses healthy donor stool to restore balance in the gut microbiome. Unlike traditional medications, FMT introduces beneficial bacteria directly into the colon, which may address the root cause of diarrhea rather than just alleviating symptoms. Researchers are excited about FMT's potential to provide a more natural and sustainable solution by restoring healthy gut flora, which might lead to faster and more effective relief for patients.

What evidence suggests that fecal microbiota transplantation is effective for immunotherapy-related diarrhea?

Research has shown that fecal microbiota transplantation (FMT), the treatment under study in this trial, effectively treats diarrhea caused by Clostridium difficile infection, achieving a 90% success rate in relieving symptoms. FMT also appears to help with diarrhea related to other medical treatments, such as cancer therapy. The process uses healthy bacteria from a donor's stool to balance the recipient's gut bacteria, supporting gut health. Early results from real-world use have confirmed FMT's effectiveness, offering hope for those with treatment-related diarrhea. Although more research is needed specifically for diarrhea related to immunotherapy, these initial findings are promising. ^{2 6 7 8 9}

Who Is on the Research Team?

David Faleck, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 who have been treated with immune checkpoint inhibitors for cancer and are experiencing persistent diarrhea (Grade 2 or higher) despite treatment. It's not suitable for those with serious heart/lung issues, an inability to handle anesthesia, pregnant women, or those planning pregnancy/breastfeeding soon.

Inclusion Criteria

I have severe diarrhea from cancer treatment that didn't improve with specific medications.

I have experienced severe diarrhea due to immune checkpoint inhibitor therapy.

I have been treated with immune therapy for cancer.

Exclusion Criteria

I cannot undergo anesthesia due to serious heart/lung issues or intolerance.

I do not have an active infection in my digestive system.

Pregnancy: Patient is pregnant, Women of childbearing potential should not have plans to become pregnant or breastfeed an infant and must agree to use a highly effective method of birth control until 2 months after treatment with FMT (e.g. barrier method, oral or parenteral contraceptives, a vasectomized partner, or abstinence from sexual intercourse)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo fecal microbiota transplantation (FMT) during a colonoscopy procedure to treat ICI-related diarrhea

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after FMT, with adverse events tracked for 7 days post-procedure

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Fecal Microbiota Transplantation (FMT)

Trial Overview The study is examining fecal microbiota transplantation (FMT), where stool from a healthy donor is infused into the patient's intestines via colonoscopy. The goal is to restore healthy bacteria balance and alleviate ICI-related diarrhea.

How Is the Trial Designed?

Group I: Fecal Microbiota Transplantation (FMT) Experimental Treatment 1 Intervention

Study subjects will undergo standard bowel preparation and diagnostic colonoscopy with routine biopsies for pathologic assessment. FMT will be performed at the proximal extent of the colon reached, according to the same protocol used in prior randomized studies. FMT will use healthy donor stool provided by OpenBiome, a nonprofit 501(c)(3) organization that provides clinicians and hospitals with screened, filtered and frozen stool to be used for FMT. Routine clinical and research biopsies will be collected during the FMT colonoscopy procedure.

Fecal Microbiota Transplantation (FMT) is already approved in European Union, United States for the following indications:

Approved in European Union as Fecal Microbiota Transplantation for:

• Recurrent Clostridium difficile infection

Approved in United States as Fecal Microbiota Transplantation for:

• Recurrent Clostridium difficile infection

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

Fecal microbiota transplant (FMT) is an effective treatment for recurrent Clostridioides difficile infections, highlighting its established role in restoring gut health.

There is growing interest in exploring FMT's potential benefits for other gastrointestinal diseases linked to dysbiosis, suggesting it may have broader therapeutic applications beyond just C. difficile infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplant, its usefulness beyond Clostridioides difficile in gastrointestinal diseases. Núñez F, P., Quera, R., Bay, C., et al.[2022]

Fecal microbiota transplantation (FMT) showed significant long-term efficacy in reducing IBS symptoms, with response rates of 69.1% and 77.8% for the 30g and 60g treatment groups, respectively, at 2 years, and 64.9% and 71.8% at 3 years, compared to only 26.3% in the placebo group.

No long-term adverse events were reported, indicating that FMT is a safe intervention for IBS, with improvements in quality of life and a decrease in dysbiosis index observed in the treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. El-Salhy, M., Winkel, R., Casen, C., et al.[2022]

Fecal microbiota transplantation (FMT) is a safe and effective treatment for dysbiosis in children, with a primary clinical remission rate of 72.9% observed after the procedure.

While most adverse events (AEs) were self-limiting and occurred shortly after FMT, the long-term efficacy of FMT decreased over time, suggesting that multiple FMTs may be necessary for recurrent conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of fecal microbiota transplantation in 74 children: A single-center retrospective study. Zou, B., Liu, SX., Li, XS., et al.[2022]

Fecal microbiota transplantation (FMT) is highly effective for treating Clostridium difficile infection (CDI), with a 90% resolution of diarrhea reported in 867 patients across 33 studies, and a 94% resolution after repeated FMT in a randomized controlled trial with 16 participants.

FMT shows promise in treating ulcerative colitis, with remission rates varying from 0% to 68% in 106 patients, while its efficacy in Crohn's disease, chronic constipation, pouchitis, and irritable bowel syndrome remains inconclusive due to limited data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. Rossen, NG., MacDonald, JK., de Vries, EM., et al.[2022]

Fecal microbiota transplantation (FMT) was successfully performed in two immunocompromised children with refractory diarrhea, leading to symptom remission without any infectious complications.

The procedure resulted in the reconstruction of a diverse microbiota, indicating that FMT is a safe and effective treatment option for managing diarrhea in immunocompromised patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation for refractory diarrhea in immunocompromised diseases: a pediatric case report. Zhong, S., Zeng, J., Deng, Z., et al.[2020]

Fecal microbiota transplantation (FMT) is a therapeutic procedure that involves transferring fecal matter from a healthy donor to treat diseases, particularly recurrent Clostridium difficile infections.

Recent research highlights the importance of the human microbiome, showing that the complex mixture of microorganisms in our bodies plays a crucial role in overall health and disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intestinal microbiota and the efficacy of fecal microbiota transplantation in gastrointestinal disease. Aroniadis, OC., Brandt, LJ.[2022]

Fecal microbiota transplantation (FMT) is a cost-effective treatment for recurrent Clostridium difficile infection (rCDI), with all economic evaluations showing it to be more cost-effective than other standard treatments at a threshold of ≤$50,000 per quality-adjusted life year (QALY).

The systematic review included 9 high-quality economic evaluations, primarily focusing on rCDI and inflammatory bowel disease (IBD), indicating that while FMT is effective for rCDI, further studies are needed to explore its economic impact for other conditions like IBD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of economic evaluation in fecal microbiota transplantation. Stalder, T., Kapel, N., Diaz, S., et al.[2021]

Fecal microbiota transplantation (FMT) showed a high efficacy rate in elderly patients with recurrent Clostridium difficile infection, with 90% of FMT patients improving within 3 days compared to only 39% in the conventional treatment group.

While FMT is effective, there are safety concerns, as two patients experienced significant adverse events during the procedure, suggesting that colonoscopy may be the safer method for administering FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Transplantation for Treatment of Clostridium Difficile Infection in Elderly and Debilitated Patients. Friedman-Korn, T., Livovsky, DM., Maharshak, N., et al.[2020]

Faecal microbiota transplantation (FMT) has proven effective for treating recurrent Clostridium difficile infections, with established protocols and donor stool banks in Denmark.

However, FMT is not recommended for routine use in treating inflammatory bowel disease or irritable bowel syndrome due to insufficient clinical trial data supporting its efficacy for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Faecal microbiota transplantation for the treatment of bowel disease]. Rode, AA., Chehri, M., Petersen, AM., et al.[2019]

Fecal microbiota transplantation (FMT) is recommended for treating recurrent Clostridium difficile infections and has shown benefits for various gastrointestinal disorders, but safety data is still limited due to the rapid adoption of the technique without extensive long-term studies.

Capsulized FMT therapy offers a promising solution for long-term maintenance and reduces the need for invasive procedures, indicating a shift towards safer and more tolerable methods of delivering FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current research progress and thinking of fecal microbiota transplantation for the treatment of gastrointestinal disorders]. Li, N., Tian, H.[2020]

Fecal microbiota transplantation (FMT) has a total adverse event (AE) incidence rate of 28.5%, with abdominal discomfort being the most common AE reported in 19 studies, highlighting the need for careful monitoring during the procedure.

Serious adverse events (SAEs) occurred in 9.2% of patients, with a notable incidence of death (3.5%) and infections (2.5%), indicating that while FMT can be beneficial, it carries significant risks that require further investigation through high-quality randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review: Adverse Events of Fecal Microbiota Transplantation. Wang, S., Xu, M., Wang, W., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8034505/

Fecal Microbiota Transplantation Is Highly Effective in Real ... Fecal microbiota transplantation is highly effective in real-world practice: Initial results from the FMT National Registry.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0305737225001471

Fecal microbiota transplantation to enhance cancer ... This systematic review evaluates Fecal Microbiota Transplantation (FMT)'s impact on cancer treatment outcomes and treatment-related toxicity and ...

3. withpower.com withpower.com/trial/phase-1-diarrhea-4-2021-f3855

Stool Transplant for Immunotherapy-Related Diarrhea Fecal microbiota transplantation (FMT) is highly effective for treating Clostridium difficile infection (CDI), with a 90% resolution of diarrhea reported in ...

4. gutpathogens.biomedcentral.com gutpathogens.biomedcentral.com/articles/10.1186/s13099-025-00705-4

Fecal microbiota transplantation alleviates ... - Gut Pathogens Fecal microbiota transplantation alleviates immunosuppressant-associated diarrhea and recurrent urinary tract infection in kidney transplant ...

5. en.wikipedia.org en.wikipedia.org/wiki/Fecal_microbiota_transplant

Fecal microbiota transplant ^ "Effectiveness of Fecal Microbiota Transplantation ... faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9229182/

Fecal Microbiota Transplantation Effectively Cures a ... We report a case of successful treatment of PD-1 inhibitor-associated colitis with fecal microbiota transplantation (FMT).

7. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1439176/full

Safety and efficacy of fecal microbiota transplantation (FMT ... Reported adverse events include self-limiting conditions like nausea, abdominal pain, and FMT-related diarrhea (186). ... fecal microbiota transplant therapy in ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11883108/

Fecal microbiota transplantation for the treatment of intestinal ... This review gathered and summarized application of FMT in intestinal diseases, metabolic diseases, hypertension, cancer, nervous system diseases and arthritis

9. sciencedirect.com sciencedirect.com/science/article/pii/S1931312824002749

From poo to promise: Fecal microbiota transplants support ... In Translation. From poo to promise: Fecal microbiota transplants support immunotherapy re-sensitization in solid tumors.