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

Trial Summary

What is the purpose of this trial?

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.

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 data supports the idea that Fecal Microbiota Transplantation for Genitourinary Cancers is an effective treatment?

The available research shows that Fecal Microbiota Transplantation (FMT) is primarily used for treating recurrent Clostridium difficile infections, and there is insufficient evidence to recommend it for other diseases, including genitourinary cancers. While FMT has been explored for various conditions like ulcerative colitis and metabolic syndrome, more research is needed to determine its effectiveness for cancer patients. Therefore, there is currently no strong data supporting FMT as an effective treatment for genitourinary cancers. ^{1 2 3 4 5}

What safety data exists for Fecal Microbiota Transplantation?

The safety of Fecal Microbiota Transplantation (FMT) has been evaluated in various studies, primarily focusing on its use for gastrointestinal conditions like ulcerative colitis. Systematic reviews and meta-analyses have assessed the safety of FMT, indicating it is generally considered safe for these conditions. Additionally, there is a case report of FMT being used in a kidney transplant recipient for recurrent urinary tract infections, suggesting its application beyond gastrointestinal issues. However, specific safety data for genitourinary cancers is not directly addressed in the provided research. ^{1 6 7 8 9}

Is Fecal Microbiota Transplantation a promising treatment for genitourinary cancers?

Fecal Microbiota Transplantation (FMT) is a promising treatment because it has shown potential in treating various diseases, including infections and possibly cancer. It works by introducing healthy bacteria into the body, which can help fight infections and improve health. Some studies suggest it might also help with urinary tract infections and cancer, making it a promising option for genitourinary cancers. ^{1 2 5 10 11}

Research Team

Yinghong Wang

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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 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]

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) 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 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) 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 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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in a kidney transplant recipient with recurrent urinary tract infection. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in patients with cancer undergoing treatment. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Low Level Engraftment and Improvement following a Single Colonoscopic Administration of Fecal Microbiota to Patients with Ulcerative Colitis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in disease therapy. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

An updated systematic review and meta-analysis of fecal microbiota transplantation for the treatment of ulcerative colitis. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Findings From a Randomized Controlled Trial of Fecal Transplantation for Patients With Ulcerative Colitis. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Intestinal microbiota and the efficacy of fecal microbiota transplantation in gastrointestinal disease. [2022]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Early Economic Assessment of Faecal Microbiota Transplantation for Patients with Urinary Tract Infections Caused by Multidrug-Resistant Organisms. [2023]