FMT + Immunotherapy for Non-Small Cell Lung Cancer or FMT + Immunotherapy for Melanoma

(FMT-LUMINATE Trial)

Recruiting at 5 trial locations

Overseen By Arielle Elkrief, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Must not be taking: Antibiotics, Probiotics, Corticosteroids

Disqualifiers: Pregnancy, Immunodeficiency, Autoimmune, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 2

Duration: Up to 2 years

45 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is evaluating whether fecal microbiota transplantation (FMT) can be used to treat cancer.

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 use probiotics during the treatment and must stop them at least 24 hours before starting. Also, you cannot have used antibiotics within 2 weeks before joining the study.

What data supports the effectiveness of the treatment FMT + Immunotherapy for Non-Small Cell Lung Cancer or Melanoma?

Research shows that fecal microbiota transplantation (FMT) is highly effective for treating Clostridium difficile infections and has potential in cancer treatment by improving the response to immunotherapy. Early trials combining FMT with immune therapies have shown promising results, suggesting it might help overcome resistance to cancer treatments. ^{1 2 3 4 5}

Is Fecal Microbiota Transplantation (FMT) safe for humans?

FMT is generally considered safe and well-tolerated, even in high-risk patients, with most short-term risks being mild. However, long-term side effects are not well-established, and serious adverse events have been linked to inadequate screening for multi-drug resistant organisms in some cases. ^{6 7 8 9 10}

How does the FMT + Immunotherapy treatment differ from other treatments for non-small cell lung cancer or melanoma?

This treatment is unique because it combines fecal microbiota transplantation (FMT) with immunotherapy to potentially enhance the effectiveness of cancer treatment by modulating the gut microbiome, which can influence the body's immune response to cancer. Unlike traditional treatments, this approach aims to overcome resistance to immunotherapy by altering the gut bacteria composition, which is a novel strategy in cancer care. ^{1 2 3 4 11}

Research Team

Arielle Elkrief, MD

Principal Investigator

CHUM

Eligibility Criteria

Adults over 18 with certain types of advanced melanoma or non-small cell lung cancer (NSCLC) that haven't been treated with anti-PD1 drugs. They must understand the risks of fecal microbial transplantation (FMT), not have autoimmune diseases, active infections, severe heart conditions, or be pregnant. Participants should not be on high-dose steroids and must agree to effective contraception.

Inclusion Criteria

My condition is at stage IV or cannot be surgically removed.

I have never received anti-PD1 treatment.

My melanoma returned more than 6 months after my last immunotherapy.

Exclusion Criteria

I have an active inflammatory bowel condition.

I have not taken antibiotics in the last 2 weeks.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive immune checkpoint inhibitor (ICI) therapy in combination with fecal microbial transplantation (FMT).

Up to 2 years

Every 2-4 weeks depending on treatment regimen

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

Treatment Details

Interventions

• Fecal Microbial Transplantation

Trial Overview The trial is testing the combination of FMT and immune checkpoint inhibitors (ICI) as a treatment for advanced melanoma and NSCLC. It aims to see if adding FMT can boost the anti-tumor effects of ICI therapy in patients who meet specific health criteria.

Participant Groups

Group I: Immune checkpoint inhibitor (ICI) therapy in combination with fecal microbial transplantation (FMT). Experimental Treatment 1 Intervention

Metastatic or advanced NSCLC: Single-agent Pembrolizumab (2 mg/kg or 200 mg every 3 weeks) in combination with investigational FMT capsules as follows: Full FMT at least 7 days prior to first cycle of Pembrolizumab. Metastatic melanoma and uveal melanoma: Combination therapy of Ipilimumab plus Nivolumab (Ipilimumab 3 mg/kg every 3 weeks and Nivolumab 1 mg/kg every 3 weeks x 4 doses, followed by Nivolumab 3 mg/kg or 240mg every 2 weeks or 6 mg/kg or 480mg every 4 weeks) in combination with investigational FMT capsules as follows: full FMT at least 7 days prior to first treatment with Ipilimumab plus Nivolumab, followed by supportive FMT within 7 days of the second cycle with combination Ipilimumab plus Nivolumab, followed by supportive FMT within 7 days of the third cycle of Ipilimumab plus Nivolumab.

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Findings from Research

Fecal microbiota transplantation (FMT) shows a higher response rate compared to medical therapy (MT) specifically for recurrent Clostridium difficile infections (RCDI), suggesting it may be a more effective treatment option for these patients.

However, FMT does not demonstrate a significant advantage over MT for treating primary Clostridium difficile infections (CDI), indicating that FMT should not be used universally for all CDI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation and Medical Therapy for Clostridium difficile Infection : Meta-analysis of Randomized Controlled Trials. Singh, T., Bedi, P., Bumrah, K., et al.[2023]

The gut microbiota plays a significant role in cancer treatment, particularly in enhancing the effectiveness of immune checkpoint inhibitors (ICIs), as shown by metagenomic profiling and murine studies.

Fecal microbiota transplantation (FMT) shows promise as a novel therapeutic strategy when combined with ICIs, although safety concerns and challenges related to pathogen transmission need to be addressed before it can be widely adopted in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future indications and clinical management for fecal microbiota transplantation (FMT) in immuno-oncology. Jamal, R., Messaoudene, M., de Figuieredo, M., et al.[2023]

Fecal microbiota transplantation (FMT) was performed on 26 patients with recurrent Clostridium difficile infection, showing a 92% success rate in preventing further diarrhea or CDI relapse over a follow-up period of up to 30 months.

The procedure was found to be simple and safe, with most patients remaining free of significant diarrhea after the treatment, highlighting FMT as a promising alternative to prolonged antibiotic courses for managing recurrent CDI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation for relapsing Clostridium difficile infection in 26 patients: methodology and results. Kelly, CR., de Leon, L., Jasutkar, N.[2022]

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) was successfully performed in two immunocompromised children with refractory diarrhea, leading to symptom remission without any infectious complications.

The procedure resulted in the reconstruction of a diverse microbiota, indicating that FMT is a safe and effective treatment option for managing diarrhea in immunocompromised patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation for refractory diarrhea in immunocompromised diseases: a pediatric case report. Zhong, S., Zeng, J., Deng, Z., et al.[2020]

Fecal microbiota transplantation (FMT) is a safe and effective treatment for dysbiosis in children, with a primary clinical remission rate of 72.9% observed after the procedure.

While most adverse events (AEs) were self-limiting and occurred shortly after FMT, the long-term efficacy of FMT decreased over time, suggesting that multiple FMTs may be necessary for recurrent conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of fecal microbiota transplantation in 74 children: A single-center retrospective study. Zou, B., Liu, SX., Li, XS., 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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Fecal Microbiota Transplantation and Medical Therapy for Clostridium difficile Infection : Meta-analysis of Randomized Controlled Trials. [2023]

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

Future indications and clinical management for fecal microbiota transplantation (FMT) in immuno-oncology. [2023]

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

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

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

Fecal microbiota transplantation for relapsing Clostridium difficile infection in 26 patients: methodology and results. [2022]

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

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

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

Fecal microbiota transplantation for refractory diarrhea in immunocompromised diseases: a pediatric case report. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of fecal microbiota transplantation in 74 children: A single-center retrospective study. [2022]

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

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

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

Fecal Microbiota Transplantation: Is It Safe? [2021]

11. Switzerland pubmed.ncbi.nlm.nih.gov

The Gut Microbiome and Cancer Immunotherapy: Can We Use the Gut Microbiome as a Predictive Biomarker for Clinical Response in Cancer Immunotherapy? [2021]