Fecal Microbial Transplantation in Combination With Immunotherapy in Melanoma Patients (MIMic)

NCT ID: NCT03772899

Last Updated: 2025-03-28

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-27
• Study Completion Date: 2026-08-31

Brief Summary

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.

Conditions

Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Study Intervention

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

Group Type: EXPERIMENTAL

Fecal Microbial Transplantation

Intervention Type: DRUG

All patients in this trial will receive FMT at least one week prior to treatment with approved immunotherapy (either pembrolizumab or nivolumab). Samples for FMT are sourced at and by the microbiology group under the supervision of Dr. Silverman at St Joseph's Hospital. Donor screening procedures are described in appendix 4. Transplant will be from one single donor for all participants unless Dr. Silverman's lab considers the need for more than one donor based on availability of donors. There will be no "mixture" of donor samples.

Donor samples are manufactured into capsules according to Kao et al, 2017.

Interventions

Fecal Microbial Transplantation

All patients in this trial will receive FMT at least one week prior to treatment with approved immunotherapy (either pembrolizumab or nivolumab). Samples for FMT are sourced at and by the microbiology group under the supervision of Dr. Silverman at St Joseph's Hospital. Donor screening procedures are described in appendix 4. Transplant will be from one single donor for all participants unless Dr. Silverman's lab considers the need for more than one donor based on availability of donors. There will be no "mixture" of donor samples.

Donor samples are manufactured into capsules according to Kao et al, 2017.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients must be 18-years old or older
• Patients must have a confirmed diagnosis of unresectable or metastatic cutaneous melanoma (BRAF wild type or mutant)
• Patients with ECOG performance of 0-2
• Patients must be able to provide written informed consent and understand the infectious risks associated with FMT administration
• Must understand non-infectious risks associated with FMT administration
• Ability to ingest capsules
• Understand that data regarding the long-term safety risk of FMT are lacking
• Patients receiving systemic steroids at physiologic doses are permitted to enroll assuming steroid dose is not above the acceptable threshold (> 10 mg prednisone daily or equivalent)
• Have measurable disease as per RECIST version 1.1

Exclusion Criteria

• Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Current or recent [in the last 90 days] exposure to high dose oral or IV corticosteroids

o Patients who require intermittent use of bronchodilators or local steroid injections are not excluded from the study

• Has a diagnosis of immunodeficiency (e.g. HIV, transplantation) or receiving systemic steroid therapy (>10mg prednisone daily or equivalent) or any other form of immunosuppressive therapy prior to trial treatment
• Ongoing use of antibiotics or previous use of antibiotics in the last two weeks prior to the FMT procedure
• Presence of a chronic intestinal disease (e.g. Celiac, malabsorption, colonic tumor)
• Presence of absolute contra-indications to FMT administration

• Toxic megacolon
• Severe dietary allergies (e.g. shellfish, nuts, seafood)
• Inflammatory bowel disease
• Anatomic contra-indications to colonoscopy
• Expected to require any other form of systemic or localized anti-neoplastic therapy while on study
• Has a known history of a hematologic malignancy, primary brain tumor or sarcoma, or of another primary solid tumor, unless the patient has undergone potentially curative therapy with no evidence of that disease for five years

o NOTE: This time requirement also does not apply to patients who underwent successful definitive resection of basal or squamous cell carcinoma of the skin, superficial bladder cancer, in situ cancers including cervical cancer, breast cancer, melanoma, or other in situ cancers.

• Active central nervous system (CNS) metastases and/or leptomeningeal involvement
• Patients with leptomeningeal disease (leptomeningeal enhancement on MRI/CT imaging and/or positive CSF cytology)
• Has an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents.

o Patients with vitiligo, type I diabetes, resolved childhood asthma/atopy are exceptions to this rule

• A history of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Has serious concomitant illnesses, such as: cardiovascular disease (uncontrolled congestive heart failure, hypertension, cardiac ischemia, myocardial infarction, and severe cardiac arrhythmia), bleeding disorders, autoimmune diseases, severe obstructive or restrictive pulmonary diseases, active systemic infections, and inflammatory bowel disorders

o This includes HIV or AIDS-related illness, or active HBV and HCV

• Has an active infection requiring systemic therapy.
• Patient has received a live vaccine within 4 weeks prior to the first dose of treatment

o Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

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

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John Lenehan, MD

Role: PRINCIPAL_INVESTIGATOR

London Regional Cancer Program

Locations

London Regional Cancer Program

London, Ontario, Canada

CHUM

Montréal, Ontario, Canada

Jewish General Hospital

Montreal, Quebec, Canada

Countries

Canada

References

Routy B, Lenehan JG, Miller WH Jr, Jamal R, Messaoudene M, Daisley BA, Hes C, Al KF, Martinez-Gili L, Puncochar M, Ernst S, Logan D, Belanger K, Esfahani K, Richard C, Ninkov M, Piccinno G, Armanini F, Pinto F, Krishnamoorthy M, Figueredo R, Thebault P, Takis P, Magrill J, Ramsay L, Derosa L, Marchesi JR, Parvathy SN, Elkrief A, Watson IR, Lapointe R, Segata N, Haeryfar SMM, Mullish BH, Silverman MS, Burton JP, Maleki Vareki S. Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial. Nat Med. 2023 Aug;29(8):2121-2132. doi: 10.1038/s41591-023-02453-x. Epub 2023 Jul 6.

Reference Type: DERIVED

PMID: 37414899 (View on PubMed)

Other Identifiers

MIMic

Identifier Type: -

Identifier Source: org_study_id