Fecal Microbiota Transplantation for Skin Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Yinghong Wang

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: M.D. Anderson Cancer Center

Must be taking: Immunosuppressive agents

Disqualifiers: Under 18, Inflammatory bowel disease, Pregnancy, Active infection, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial studies the role of the gut microbiome and effectiveness of a fecal transplant on medication-induced gastrointestinal (GI) complications in patients with melanoma or genitourinary cancer. The gut microbiome (the bacteria and microorganisms that live in the digestive system) may affect whether or not someone develops colitis (inflammation of the intestines) during cancer treatment with immune-checkpoint inhibitor drugs. Studying samples of stool, blood, and tissue from patients with melanoma or genitourinary cancer may help doctors learn more about the effects of treatment on cells, and help doctors understand how well patients respond to treatment. Treatment with fecal transplantation may help to improve diarrhea and colitis symptoms.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants may be on immunosuppressive agents like steroids, infliximab, vedolizumab, or ustekinumab during the study.

Is fecal microbiota transplantation (FMT) generally safe for humans?

Fecal microbiota transplantation (FMT) is generally considered safe and well-tolerated, especially for treating recurrent Clostridioides difficile infections. Most short-term risks are mild and related to the delivery method, but long-term safety data is limited. Serious adverse events have been linked to inadequate donor screening, highlighting the importance of strict protocols. ^{1 2 3 4 5}

How is fecal microbiota transplantation (FMT) different from other treatments for skin cancer?

FMT is unique because it involves transferring healthy bacteria from a donor's stool to a patient's gut to restore balance in the intestinal microbiota, which is different from traditional cancer treatments like chemotherapy or radiation that directly target cancer cells. ^{6 7 8 9 10}

Research Team

Yinghong Wang

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with melanoma, non-small cell lung cancer, or genitourinary cancers who are experiencing gastrointestinal issues due to immune-checkpoint inhibitor drugs. They must not have an active GI infection and should have a life expectancy over 4 months. Pregnant women and those under 18 are excluded.

Inclusion Criteria

I have been treated with immune checkpoint inhibitors.

I have been diagnosed with melanoma, lung cancer, or a genitourinary cancer.

I have had severe colitis or diarrhea from cancer treatment that hasn't improved with standard treatments.

Exclusion Criteria

I am under 18 years old.

I can choose to leave the trial at any time.

I do not have an active bacterial or fungal infection.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Standard of Care and Sample Collection

Patients receive standard of care and undergo collection of stool and blood samples

Up to 1 year

Medical Treatment and Endoscopy

Patients receive prednisone, infliximab, or vedolizumab and undergo standard of care endoscopy 2 months after treatment

2 months

Fecal Microbiota Transplantation (FMT)

Patients undergo fecal microbiota transplant

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Treatment Details

Interventions

• Fecal Microbiota Transplantation (Fecal Microbiota Transplantation)
• Infliximab (Monoclonal Antibodies)
• Prednisone (Corticosteroid)
• Vedolizumab (Monoclonal Antibodies)

Trial Overview The study is testing how the gut microbiome affects colitis caused by cancer treatments and if fecal transplants can improve symptoms. It involves analyzing stool, blood, tissue samples from patients, and comparing these with standard treatments like steroids or other immunosuppressants.

Participant Groups

Group I: Supportive Care (standard of care, sample collection, FMT) Experimental Treatment 8 Interventions

PROJECT 1: Patients receive standard of care and undergo collection of stool and blood samples. PROJECT 2: Patients receive prednisone, infliximab, or vedolizumab per standard of care and undergo standard of care endoscopy 2 months after treatment. Patients also undergo collection of stool, blood, and tissue samples. PROJECT 3: Patients undergo FMT.

Fecal Microbiota Transplantation is already approved in Canada for the following indications:

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+

Dr. Peter WT Pisters

M.D. Anderson Cancer Center

Chief Executive Officer since 2017

MD from University of Western Ontario

Dr. Jeffrey E. Lee

M.D. Anderson Cancer Center

Chief Medical Officer

MD from Stanford University School of Medicine

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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) is a safe and effective treatment for recurrent Clostridioides difficile infections, highlighting its importance in clinical practice.

The selection of fecal microbiota donors is crucial for ensuring the safety of recipients, prompting the establishment of protocols and recommendations by a multidisciplinary group in Cataluña to minimize risks associated with the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recommendations for stool donor selection for fecal microbiota transplant. Consensus document endorsed by the Catalan Society of Digestology, Catalan Society of Infectious diseases and Clinical Microbiology and the GEMBIOTA group from Spanish Society of Infectious Diseases and Clinical Microbiology. Aira, A., Arajol, C., Casals-Pascual, C., et al.[2022]

Fecal microbiota transplantation (FMT) is a generally safe and well-tolerated procedure for treating recurrent Clostridioides difficile infections, even in high-risk patients, with most short-term risks being mild and related to delivery methods.

Recent concerns have emerged regarding serious adverse events linked to FMT products from stool banks that do not screen for multi-drug resistant organisms, highlighting the need for improved safety protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation: Is It Safe? Park, SY., Seo, GS.[2021]

Fecal microbiota transplantation (FMT) has a reported adverse event (AE) rate of 39.3%, primarily involving mild and self-limiting issues like abdominal pain and diarrhea, based on a meta-analysis of 9 high-quality studies involving 756 FMTs.

Serious adverse events (SAE) were relatively rare at 5.3%, with the most common being Clostridium difficile infection, indicating that while FMT is generally safe, monitoring and standardized reporting are essential for understanding its long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of fecal microbiota transplantation: a meta-analysis of high-quality studies. Michailidis, L., Currier, AC., Le, M., 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]

Faecal microbiota transplantation (FMT) has shown effectiveness in inducing remission in active ulcerative colitis (UC), with a clinical remission rate of 28% in FMT patients compared to 9% in placebo groups based on a meta-analysis of randomized controlled trials involving 277 patients.

The study found no major short-term safety concerns associated with FMT, suggesting it is a safe option for patients with UC, although further research is needed to optimize treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review with meta-analysis: faecal microbiota transplantation for the induction of remission for active ulcerative colitis. Costello, SP., Soo, W., Bryant, RV., et al.[2022]

In 2019, 31 FMT centers across 17 European countries performed a total of 1,874 fecal microbiota transplants, primarily for Clostridioides difficile infection (CDI), indicating that FMT is a common treatment for this condition.

Despite the high safety standards and adherence to guidelines observed in these centers, only about 10% of the estimated patients needing FMT for recurrent CDI in Europe received the treatment, highlighting a significant gap in coverage and the need for increased clinical awareness and activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of Faecal Microbiota Transplantation (FMT) in Europe: A Europe-wide survey. Baunwall, SMD., Terveer, EM., Dahlerup, JF., et al.[2022]

Fecal microbiota transplantation (FMT) is an effective treatment for restoring healthy gut bacteria in patients with disrupted intestinal microbiota, particularly in conditions like Clostridium difficile infection.

The review emphasizes the importance of careful donor selection and proper processing and storage of fecal material to ensure the safety and efficacy of the transplantation procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fecal microbiota transplantation: donor selection criteria, storage and preparation of biomaterials (review of current recommendations)]. Iakupova, AA., Abdulkhakov, SR., Safin, AG., et al.[2022]

Fecal microbiota transplant (FMT) from tumor-bearing mice significantly improved cognitive function and short-term memory in Alzheimer's disease (AD) mice, indicating a potential therapeutic role for gut microbiota in cognitive impairment.

The FMT not only reduced Aβ plaque burden in the brain but also altered the gut microbiome composition, reversing specific microbial imbalances associated with AD, suggesting a complex interaction between gut health and cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transfer of Tumor-Bearing Mice Intestinal Flora Can Ameliorate Cognition in Alzheimer's Disease Mice. Hang, Z., Cai, S., Lei, T., et al.[2022]

In a study of 27 patients with therapy-refractory ulcerative colitis, faecal microbiota transplantation (FMT) resulted in a 59% response rate and a 24% remission rate, indicating its potential effectiveness as a treatment.

The success of FMT was significantly influenced by the donor's microbiota composition, particularly higher bacterial richness and specific beneficial bacteria like Akkermansia muciniphila, suggesting that tailored donor selection could enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The taxonomic composition of the donor intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in therapy refractory ulcerative colitis. Kump, P., Wurm, P., Gröchenig, HP., et al.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

[Current research progress and thinking of fecal microbiota transplantation for the treatment of gastrointestinal disorders]. [2020]

2. Spain pubmed.ncbi.nlm.nih.gov

Recommendations for stool donor selection for fecal microbiota transplant. Consensus document endorsed by the Catalan Society of Digestology, Catalan Society of Infectious diseases and Clinical Microbiology and the GEMBIOTA group from Spanish Society of Infectious Diseases and Clinical Microbiology. [2022]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation: Is It Safe? [2021]

4. Greece pubmed.ncbi.nlm.nih.gov

Adverse events of fecal microbiota transplantation: a meta-analysis of high-quality studies. [2022]

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

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

6. England pubmed.ncbi.nlm.nih.gov

Systematic review with meta-analysis: faecal microbiota transplantation for the induction of remission for active ulcerative colitis. [2022]

7. England pubmed.ncbi.nlm.nih.gov

The use of Faecal Microbiota Transplantation (FMT) in Europe: A Europe-wide survey. [2022]

8. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Fecal microbiota transplantation: donor selection criteria, storage and preparation of biomaterials (review of current recommendations)]. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Transfer of Tumor-Bearing Mice Intestinal Flora Can Ameliorate Cognition in Alzheimer's Disease Mice. [2022]

10. England pubmed.ncbi.nlm.nih.gov

The taxonomic composition of the donor intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in therapy refractory ulcerative colitis. [2022]