Fecal Microbiota Transplantation for Genitourinary Cancers

Overseen By Yinghong Wang

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must be taking: Immune checkpoint inhibitors

Must not be taking: Immunosuppressive treatments

Disqualifiers: Age < 18, Pregnancy, IBD, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 day

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether fecal microbiota transplantation (FMT) can treat diarrhea or colitis (inflammation of the intestines) caused by immune-checkpoint inhibitors, a type of cancer medication. FMT involves transplanting healthy bacteria from a donor's stool into the patient’s gut to improve intestinal health. It may benefit those with genitourinary cancer who experience significant diarrhea or colitis due to these medications. Participants should not have active GI infections and must have been free from immunosuppressive treatments when symptoms began. As a Phase 1 trial, this research aims to understand how FMT works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop your current medications. However, if you have used steroids, you must have stopped them more than 30 days before the treatment, and if you have used immunosuppressants like Infliximab or Vedolizumab, you must have stopped them at least 3 months before the treatment.

What prior data suggests that fecal microbiota transplantation is safe for treating diarrhea or colitis in genitourinary cancer patients?

Research has shown that fecal microbiota transplantation (FMT) is generally safe and well-tolerated. Long-term data from a study in Hong Kong indicated that patients who received FMT over eight years did not experience major safety issues. Another study found that using donor FMT alongside cancer treatments is both safe and practical.

A national registry monitors thousands of FMT patients for any short-term problems. So far, this registry has not reported any significant safety concerns. These findings suggest that FMT is safe for most people, especially when used to help manage side effects of cancer medications like immune checkpoint inhibitors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for genitourinary cancers, which often involve surgery, chemotherapy, or radiation, fecal microbiota transplantation (FMT) offers a unique approach by targeting the gut microbiome. FMT involves transplanting healthy bacteria from a donor’s fecal matter into the patient’s colon. Researchers are excited because this method could enhance the body's immune response to cancer and improve overall treatment outcomes. This innovative approach also holds the potential to reduce some side effects associated with conventional cancer therapies.

What evidence suggests that fecal microbiota transplantation is effective for treating diarrhea or colitis in genitourinary cancer patients?

Research has shown that fecal microbiota transplantation (FMT) can help treat diarrhea and colitis caused by certain cancer treatments. One study found that FMT improved gut health and reduced symptoms like diarrhea in patients experiencing these side effects. Another review suggests that FMT might enhance cancer treatment by balancing gut bacteria. Early results from a registry indicated that FMT works well in real-life situations, offering practical benefits for patients. In this trial, participants will receive FMT via colonoscopy, and these findings suggest FMT could help manage symptoms for patients with genitourinary cancers who experience these side effects. ^{1 2 3 4 6}

Who Is on the Research Team?

Yinghong Wang

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with genitourinary, melanoma, lung, ovarian, uterine, cervical or breast cancers who have diarrhea or colitis from immune-checkpoint inhibitors. They must not be pregnant/breastfeeding and should not have a high risk for colonoscopy complications or persistent GI infections.

Inclusion Criteria

I have been treated with immune checkpoint inhibitors.

I have had severe diarrhea or colitis from cancer treatment in the last 45 days.

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

Exclusion Criteria

I started immunosuppressive treatment when my diarrhea or colitis began after cancer immunotherapy.

I experienced side effects not related to my digestive system during the study treatment.

I have active inflammatory bowel disease or radiation-induced bowel inflammation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive loperamide orally and undergo fecal microbiota transplantation (FMT) via colonoscopy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Visits at 2, 4, and 8 weeks, and then at 3 months

Extension

Monitoring for recurrent immune-related diarrhea/colitis following FMT and immune checkpoint inhibitors (ICPI) resumption

Up to 6 months after restarting ICPI

What Are the Treatments Tested in This Trial?

Interventions

• Fecal Microbiota Transplantation

Trial Overview The study tests fecal microbiota transplantation (FMT) to treat immune-checkpoint inhibitor-induced diarrhea/colitis in cancer patients. It aims to see if FMT can reduce these side effects effectively compared to the standard treatment with Loperamide.

How Is the Trial Designed?

Group I: Treatment (loperamide, colonoscopy, FMT) Experimental Treatment 2 Interventions

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

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

Approved in United States as Fecal Microbiota Transplantation for:

• Graft-versus-host disease (GVHD)
• Clostridioides difficile infection (CDI)

Approved in European Union as Fecal Microbiota Transplantation for:

• Graft-versus-host disease (GVHD)
• Clostridioides difficile infection (CDI)
• Other gastrointestinal disorders

Approved in Canada as Fecal Microbiota Transplantation for:

• Graft-versus-host disease (GVHD)
• Clostridioides difficile infection (CDI)

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a double-blind randomized trial involving 50 patients with mild to moderately active ulcerative colitis, fecal microbiota transplantation (FMT) from healthy donors did not show a statistically significant improvement in clinical remission compared to autologous fecal microbiota, with 30.4% of the FMT group achieving remission versus 20.0% in the control group.

Despite the lack of significant differences in remission rates, the microbiota of patients who responded to FMT showed similarities to their healthy donors, suggesting that specific microbial profiles may be associated with treatment response and warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Findings From a Randomized Controlled Trial of Fecal Transplantation for Patients With Ulcerative Colitis. Rossen, NG., Fuentes, S., van der Spek, MJ., 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]

A kidney transplant recipient successfully treated recurrent urinary tract infections with fecal microbiota transplantation (FMT), remaining symptom-free after the procedure.

The study highlights the need for further research to understand the underlying mechanisms of how FMT works in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in a kidney transplant recipient with recurrent urinary tract infection. Biehl, LM., Cruz Aguilar, R., Farowski, F., et al.[2019]

Fecal microbiota transplantation (FMT) is primarily effective for treating recurrent Clostridium difficile infections by restoring a healthy microbiome in the colon.

Currently, there is not enough evidence to support the use of FMT for other gastrointestinal or nongastrointestinal diseases, although research is ongoing in these areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation. Vindigni, SM., Surawicz, CM.[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) was found to induce remission in 24% of patients with active ulcerative colitis (UC), compared to only 5% in the placebo group, demonstrating its efficacy as a treatment option.

The study showed no significant difference in adverse events between the FMT and placebo groups, indicating that FMT is a safe intervention for patients with UC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial. Moayyedi, P., Surette, MG., Kim, PT., et al.[2022]

Fecal microbiota transplantation (FMT) is an effective method for restoring healthy gut flora in patients suffering from Clostridium difficile infection (CDI).

There is a need for further research to understand how FMT can be safely and effectively used in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in patients with cancer undergoing treatment. Blackburn, LM., Bales, A., Caldwell, M., et al.[2020]

Fecal microbiota transplantation (FMT) is significantly more effective than placebo in achieving total remission, clinical remission, and steroid-free remission in patients with ulcerative colitis, based on a meta-analysis of 16 studies.

The safety profile of FMT is comparable to placebo, with no significant increase in serious adverse events, suggesting that FMT is a promising and safe treatment option for ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An updated systematic review and meta-analysis of fecal microbiota transplantation for the treatment of ulcerative colitis. Huang, T., Xu, J., Wang, M., et al.[2023]

In a study involving 7 patients with mild to moderate ulcerative colitis, fecal microbiota transplantation (FMT) achieved a donor similarity index (DSI) of 40-50% in about two-thirds of recipients, indicating some level of microbiota engraftment.

Despite achieving this level of engraftment, only one patient experienced a temporary clinical improvement, suggesting that while FMT can alter the microbiota, its efficacy in achieving lasting remission in ulcerative colitis may require further investigation and optimization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Level Engraftment and Improvement following a Single Colonoscopic Administration of Fecal Microbiota to Patients with Ulcerative Colitis. Damman, CJ., Brittnacher, MJ., Westerhoff, M., et al.[2022]

Fecal microbiota transplantation (FMT) is primarily used to treat gastrointestinal diseases caused by harmful microorganisms, but it is also being explored for conditions like metabolic syndrome, diabetes, cancer, and Parkinson's disease.

The review discusses the effects of FMT on weight gain, immune response, and various diseases, while also addressing potential side effects that recipients may experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in disease therapy. Antushevich, H.[2020]

Faecal microbiota transplantation (FMT) significantly reduced the occurrence of multidrug-resistant organism (MDRO)-related urinary tract infections (UTIs) in a cohort of five patients, with the median number of UTIs per patient dropping from 4 to 0 over a follow-up period of up to 320 days.

The use of FMT also led to a substantial decrease in hospital-related costs, with hospital admission days reduced by 87% and monthly hospital costs decreased by 79%, suggesting that FMT is a cost-effective strategy for managing recurrent UTIs in patients with MDROs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Economic Assessment of Faecal Microbiota Transplantation for Patients with Urinary Tract Infections Caused by Multidrug-Resistant Organisms. Baek, OD., Hjermitslev, CK., Dyreborg, L., 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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6767494/

Fecal microbiota transplantation in cancer management ... cancer patients by targeting gut microbiota. Keywords: gut microbiota, dysbiosis, cancer, fecal microbiota transplantation, therapy. Abbreviations. CDI.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04038619

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

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

Safety and efficacy of fecal microbiota transplantation (FMT ... Faecal microbiota transplantation to prevent complications after allogeneic stem cell transplantation for haematological Malignancies: a study protocol for ...

6. asm.org asm.org/articles/2024/february/fecal-microbiota-transplants-past-present-future

Fecal Microbiota Transplants (FMT): Past, Present and ... There is a national registry that aims to track 4,000 patients receiving FMT for 10 years to “identify potential short-term adverse outcomes and to search for ...