Fecal Microbial Transplant for Melanoma

Not currently recruiting at 2 trial locations

Overseen By John Lenehan, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Must be taking: Anti-PD-1 drugs

Must not be taking: Antibiotics, Immunosuppressants

Disqualifiers: Pregnancy, Immunodeficiency, Autoimmune, 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: 16

Duration: 4-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for helping people with advanced melanoma who have not responded well to standard cancer treatments. Researchers combine a fecal microbial transplant (FMT), which introduces healthy gut bacteria from a donor, with existing immunotherapy drugs to see if it enhances the body's ability to fight cancer. The main goal is to determine the safety of this combination and its effects on the immune system and gut health. People with advanced melanoma that cannot be surgically removed and who have tried other treatments without success might be suitable for this trial. 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 approach.

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 participate if you are using antibiotics or high-dose steroids. If you are on low-dose steroids, you may still be eligible.

What prior data suggests that Fecal Microbial Transplantation is safe for melanoma patients?

Research has shown that Fecal Microbial Transplantation (FMT) is generally safe and well-tolerated. Most side effects are mild, such as stomach upset or diarrhea. FMT has been successfully used to treat bacterial infections in patients without cancer. Studies have also examined the combination of FMT with immunotherapy drugs like pembrolizumab and nivolumab to ensure safety. In these studies, the treatment did not cause serious side effects, suggesting it is a safe option for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about fecal microbial transplantation (FMT) for melanoma because it offers a completely different approach compared to standard treatments like immunotherapy or targeted therapy. FMT works by transferring healthy gut bacteria from a donor to the patient, potentially boosting the body's immune response against cancer cells. This unique mechanism could enhance the effectiveness of existing treatments or offer an alternative for patients who don't respond well to current options. Additionally, FMT is a one-time procedure that could provide benefits without the prolonged side effects often associated with traditional cancer therapies.

What evidence suggests that Fecal Microbial Transplantation could be an effective treatment for melanoma?

Research has shown that fecal microbial transplantation (FMT) can aid some melanoma patients who do not respond to immunotherapy. Studies have found that FMT can help overcome resistance to drugs like pembrolizumab and nivolumab, which treat melanoma. For instance, one study found that FMT improved the effectiveness of these drugs, with 65% of patients experiencing a reduction in their cancer. FMT changes the gut bacteria, which seems to enhance the immune system's ability to fight cancer. Although this approach is still under investigation, early results are promising. Participants in this trial will receive one dose of FMT to further explore its potential benefits. ^{1 2 4 6 7}

Who Is on the Research Team?

John Lenehan, MD

Principal Investigator

London Regional Cancer Program

Are You a Good Fit for This Trial?

This trial is for adults with advanced melanoma that can't be surgically removed. Participants must have an ECOG performance status of 0-2, indicating they are fully active or limited in physical activity but able to care for themselves. They should understand the risks of FMT and be capable of swallowing capsules. Pregnant individuals, those on high-dose steroids or immunosuppressants, recent antibiotic users, and patients with certain other health conditions cannot join.

Inclusion Criteria

My melanoma cannot be removed by surgery and may have any BRAF status.

You have a disease that can be measured according to specific guidelines.

I am taking a low dose of steroids, not more than 10 mg of prednisone daily or its equivalent.

Exclusion Criteria

I cannot receive FMT due to specific health reasons.

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

I have an immune system condition or am taking high-dose steroids or other drugs that weaken my immune system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of Fecal Microbial Transplantation (FMT) followed by immunotherapy with pembrolizumab or nivolumab

4-8 weeks

Visits at baseline, 1 week post FMT, and 2nd dose of immunotherapy (2, 3, or 4 weeks post FMT)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including microbiome, immune biomarkers, and metabolomics analysis

3 months

3 month follow-up visit

Long-term Follow-up

Participants are assessed for objective response rate and safety over an extended period

60 months

Every 12 weeks up to 60 months

What Are the Treatments Tested in This Trial?

Interventions

• Fecal Microbial Transplantation

Trial Overview The MIMic trial tests whether combining Fecal Microbial Transplantation (FMT) from a healthy donor with standard immunotherapy drugs like pembrolizumab or nivolumab improves treatment response in melanoma patients. The study will assess safety and effects on the immune system and gut microbes.

How Is the Trial Designed?

Group I: Study Intervention Experimental Treatment 1 Intervention

Fecal Microbial Transplantation - all patients registered on study will receive one dose (80-100mg) of FMT. This is a single arm, unblinded study.

Who Is Running the Clinical Trial?

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Published Research Related to This Trial

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 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]

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) 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 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 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]

In a study of 6 pediatric solid organ transplant (SOT) recipients who received fecal microbiota transplant (FMT) for recurrent Clostridioides difficile infection (CDI), the treatment showed an 83.3% success rate in preventing CDI recurrence within 2 months.

While FMT was generally safe, one serious adverse event occurred (cecal perforation) in a kidney transplant recipient, highlighting a potential increased risk for SOT patients, though no adverse events related to immunosuppression or transplant status were observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplant in Pediatric Solid Organ Transplant Recipients. Rodig, NM., Weatherly, M., Kaplan, AL., et al.[2023]

In a study comparing fecal microbiota transplantation (FMT) protocols for recurrent Clostridioides difficile infection (rCDI), a higher volume of fresh fecal filtrate (30-50 g) resulted in a significantly higher clinical success rate (98%) compared to a lower volume of frozen fecal preparation (22.7 g) which had a success rate of 64%.

Overall clinical success was achieved in 100% of patients receiving fresh fecal filtrate at Center B, while 86% of patients at Center A achieved success after potentially needing repeat FMTs, indicating that the method and amount of fecal material used in FMT can greatly impact treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Superiority of Higher-Volume Fresh Feces Compared to Lower-Volume Frozen Feces in Fecal Microbiota Transplantation for Recurrent Clostridioides Difficile Colitis. Agarwal, A., Maheshwari, A., Verma, S., et al.[2021]

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.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12359429/

Improved survival in advanced melanoma patients treated ... Combination therapy was safe, and the objective response rate (ORR) was 65%. We now report survival data based on over 3 years of follow-up.

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

Fecal microbiota transplantation to enhance cancer ... Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science, 371 (6529) (2021), pp. 595-602, 10.1126 ...

3. bmcmedicine.biomedcentral.com bmcmedicine.biomedcentral.com/articles/10.1186/s12916-025-04183-y

Microbiota boost immunotherapy? A meta-analysis dives into ... As for FMT methods, oral fecal microbiota capsules appeared to be more effective (ORR: 49%) compared to endoscopic delivery (ORR: 34%) or ...

4. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A1406

1257 Linking fecal microbiota transplant (FMT) to anti-PD-1 ... Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients. Science. 2021 Feb 5;371(6529):595–602. PMCID: ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10831174/

Fecal microbiota transplantation: no longer cinderella in ... In this review, we examine current experimental and clinical evidences supporting the FMT efficacy in boosting anti-tumour immuno-response and lessening tumour ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10854771/

The Use of Fecal Microbiota Transplant in Overcoming and ... The secondary outcome for this study is the safety of FMT use in this patient population, and the safety of combined FMT and anti-PD-1 use.

7. thelancet.com thelancet.com/journals/ebiom/article/PIIS2352-3964(24)00002-1/fulltext

Fecal microbiota transplantation: no longer cinderella in ... Results turned out that 6 out of 15 patients got clinical benefits, including one CR, 2 PR as well as three recipients presenting stable disease ...