Fecal Microbial Transplant for Melanoma

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

20 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment Fecal Microbial Transplantation for melanoma?

Research suggests that Fecal Microbiota Transplantation (FMT) can help patients with melanoma who do not respond to immunotherapy by changing the gut bacteria to improve immune responses. FMT has shown promise in treating other conditions like recurrent Clostridium difficile infection, indicating its potential to help with various diseases by altering the gut microbiome. ^{1 2 3 4 5}

Is fecal microbiota transplantation (FMT) 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, but long-term side effects are not well-established. Serious adverse events have been linked to inadequate screening for multi-drug resistant organisms in donor stool. ^{6 7 8 9 10}

How does fecal microbiota transplantation differ from other treatments for melanoma?

Fecal microbiota transplantation (FMT) is unique because it involves transferring gut bacteria from a healthy donor to a patient to potentially overcome resistance to immunotherapy in melanoma. Unlike traditional treatments that directly target cancer cells, FMT aims to modify the gut microbiome to enhance the body's immune response against cancer. ^{1 2 4 11 12}

What is the purpose of this trial?

Immunotherapy has helped many cancer patients in the last 5 years by enhancing a patient's immune system to fight cancer. Anti-Programmed Death (PD-1) immunotherapy drugs such as pembrolizumab and nivolumab remove the breaks from cancer-fighting immune cells and have been effective in treating some melanoma patients. Despite the major breakthrough of immunotherapy in oncology treatment, many patients do not respond to this new class of anti-cancer drugs. Recently, evidence suggests that the microorganisms living in a patient's intestines play a major role in modifying the response to anti-PD-1drugs. Patients who respond to these drugs have a unique and healthy group of microorganisms in their gut. Therefore, positive modification of a cancer patient's gut microorganisms to create a more diverse and healthy microbiome may improve the response to immunotherapy. One method of modifying the microbiome is Fecal Microbial Transplantation (FMT) that is already being successfully used in the clinic to treat non-cancer patients with persistent bacterial infections. In this study, the investigators will combine FMT with the approved immunotherapy drugs pembrolizumab or nivolumab that are the standard of care for the treatment of advanced melanoma. The purpose of this study is to examine the safety of combining these two therapies in melanoma patients. The investigator will use fecal material from a healthy donor selected via our stringent protocol that is Health Canada approved. In addition to assessing the safety of the combination, the investigator will also study the effect of FMT on the immune system and microbial ecosystem of the gut.

Research Team

John Lenehan, MD

Principal Investigator

London Regional Cancer Program

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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) 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 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]

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]

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 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]

References

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

Fecal transplantation in patient with metastatic melanoma refractory to immunotherapy: A case report. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic Perspectives for Microbiota Transplantation in Digestive Diseases and Neoplasia-A Literature Review. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Conversion of unresponsiveness to immune checkpoint inhibition by fecal microbiota transplantation in patients with metastatic melanoma: study protocol for a randomized phase Ib/IIa trial. [2023]

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

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

5. United States 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. [2021]

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

Fecal Microbiota Transplantation: Is It Safe? [2021]

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

Systematic Review: Adverse Events of Fecal Microbiota Transplantation. [2023]

8. Greece pubmed.ncbi.nlm.nih.gov

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

9. 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. [2021]

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

Fecal Microbiota Transplant in Pediatric Solid Organ Transplant Recipients. [2023]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in disease therapy. [2020]

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

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