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

NCT03772899 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: MIMic
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

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

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety of combining Fecal Microbial Transplantation (FMT) using intestinal bacteria existing in the stool of healthy donors with immunotherapy in melanoma patients.

  Toxicity assessments and concurrent medication review will occur at every visit throughout immunotherapy treatment. Any adverse events after FMT administration will be followed until resolution or until judged stable by the investigator.

  60 months

Secondary Outcomes (7)

• Assess Objective Response Rate

  At baseline and every 12 weeks thereafter up to 60 months

• To Evaluate the effect(s) combination FMT and immunotherapy has on the gut microbiome

  At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy (2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit

• Evaluate the effect(s) combination FMT and immunotherapy has on changes in immune blood biomarkers

  At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy(2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit

• Evaluate the effect(s) combination FMT and immunotherapy has on changes in immune blood biomarkers

  At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy(2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit

• Evaluate the effect(s) combination FMT and immunotherapy has on changes in immune blood biomarkers

  At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy(2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit

Study Arms (1)

Study Intervention

EXPERIMENTAL

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

Drug: Fecal Microbial Transplantation

Interventions

Fecal Microbial Transplantation 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.

Study Intervention

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (3)

London Regional Cancer Program

London, Ontario, N6A 5W9, Canada

Location

CHUM

Montréal, Ontario, H2X 0C1, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Related Publications (1)

• 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.

  PMID: 37414899 DERIVED

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• John Lenehan, MD

  London Regional Cancer Program

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2018
• First Posted: December 11, 2018
• Study Start: March 27, 2019
• Primary Completion: September 14, 2021
• Study Completion (Estimated): August 1, 2026
• Last Updated: March 28, 2025

Record last verified: 2025-03

Locations

CA (3)