Assessing the Tolerance and Clinical Benefit of feCAl tranSplantation in patientS With melanOma

NCT04988841 | Completed Phase 2 DMC

• 1 other identifier: APHP200133
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 5

Brief Summary

Recent studies suggest that patients with metastatic melanoma whose gut microbiome is colonized by eubiotic bacteria have a stronger anti-cancer response to anti CTLA-4 and anti PD1. The hypothesis of this research is that a pooled standardized fecal microbiome transfer (FMT) will shift melanoma patients' gut microbiome towards a composition close to that associated with a better response, and will therefore increase the response to a combination of anti CTLA-4 and anti PD1, without affecting the safety of these drugs. The present trial is the first randomized trial of FMT in patients with unresectable or metastatic melanoma. It will include patients who have neither been exposed to anti CTLA-4 nor anti PD1 or PDL-1, prior to inclusion in the study. The pooled standardized fecal microbiome transfer administered in this study is an experimental drug MaaT013, a microbiome restoration biotherapeutic, produced by MaaT Pharma, and composed of pooled-donor, full-ecosystem intestinal microbiome. The MaaT013 product has a standardized richness (in number of species present) higher than a product obtained from a mono donor (455 species approximately against 274 on average) and contains bacteria species (mentioned in the rationale) associated with better response to anti- CTLA-4 and anti PD1.

Conditions

Melanoma

Keywords

Fecal microbiome transfer; Microbiome restoration biotherapeutic; Full-ecosystem intestinal microbiome; Response to anti- CTLA-4 and anti PD1; the tumor microenvironment; Peripheral blood T cell subpopulations; Efficacy and safety of MaaT013

Outcome Measures

Primary Outcomes (1)

• To assess whether the safety of a 23-week treatment with MaaT013, combined with ipilimumab+nivolumab, is different from that of ipilimumab+nivolumab+placebo in patients with melanoma naïve to Ipilimumab and anti-PD1

  Safety will be measured by the occurrence of treatment-related adverse events of Grade 3, grade 4 and grade 5, as graded by the CTCAE v 5.0, during the 27 weeks of the trial

  During the 27 weeks of the trial.

Secondary Outcomes (14)

• To assess whether a 23-week treatment with MaaT013, combined with Ipilimumab and Nivolumab, is more efficient than Ipilimumab and Nivolumab + placebo in patients with melanoma naïve to Ipilimumab and anti PD1.

  During the 27 weeks of the trial.

• To assess changes in the tumor microenvironment in patients who have received MaaT013 and placebo ;

  During the 27 weeks of the trial.

• Changes in plasma levels of proteins or metabolites that play a role in immune activity against cancer and/or are associated with gut microbiome composition, pre and post MaaT013 or placebo

  During the 27 weeks of the trial.

• Changes in signatures of peripheral blood T or immune cells cell. T cell or other immune cells will be sorted and transcriptomic analysis will be performed to determine changes induce by MaaT013 or placebo treatment.

  During the 27 weeks of the trial.

• To assess the evolution of gut microbial members and metabolites;

  During the baseline and 9 weeks of the trial.

Study Arms (2)

Fecal microbiotherapy (MaaT013) associated to ipilimumab and nivolumab

EXPERIMENTAL

Fecal microbiotherapy MaaT013 (actif arm) enemas will be administered by nurses, at the hospital, in the dermatology department in which the patients are treated for their melanoma. Nurses will be trained to administer enemas. The enema will be administered to the patient in the left lateral position with instructions to retain it for at least 20 minutes

Drug: MaaT013; Drug: Ipilimumab; Drug: Nivolumab; Drug: MoviPrep; Drug: Normacol

fecal microbiotherapy Placebo associated to ipilimumab and nivolumab

PLACEBO COMPARATOR

Placebo fecal microbiotherapy will be administered by nurses, at the hospital, in the dermatology department in which the patients are treated for their melanoma. Nurses will be trained to administer enemas. The enema will be administered to the patient in the left lateral position with instructions to retain it for at least 20 minutes

Drug: MaaT013; Drug: Ipilimumab; Drug: Nivolumab; Drug: MoviPrep; Drug: Normacol; Drug: Placebo of Maat013

Interventions

MaaT013 DRUG

study is an experimental drug , produced by MaaT Pharma, and composed of pooled-donor, full-ecosystem intestinal microbiome (455 species approximately against 274 on average)

Also known as: fecal microbiotherapy

Fecal microbiotherapy (MaaT013) associated to ipilimumab and nivolumab; fecal microbiotherapy Placebo associated to ipilimumab and nivolumab

Ipilimumab DRUG

Anti cytotoxicT-lymphocyte-associated protein 4 ( immunothérapy)

Fecal microbiotherapy (MaaT013) associated to ipilimumab and nivolumab; fecal microbiotherapy Placebo associated to ipilimumab and nivolumab

Nivolumab DRUG

AntiPD1 ( immunothérapy)

Fecal microbiotherapy (MaaT013) associated to ipilimumab and nivolumab; fecal microbiotherapy Placebo associated to ipilimumab and nivolumab

MoviPrep DRUG

Osmotic laxative solution : patients take a single dose of two liters of Moviprep® or equivalent the night before the first administration of experimental treatment (Fecal microbiota transfer or placebo)

Also known as: Osmotic laxative solution

Fecal microbiotherapy (MaaT013) associated to ipilimumab and nivolumab; fecal microbiotherapy Placebo associated to ipilimumab and nivolumab

Normacol DRUG

hypertonic enema solution

Also known as: hypertonic enema solution

Fecal microbiotherapy (MaaT013) associated to ipilimumab and nivolumab; fecal microbiotherapy Placebo associated to ipilimumab and nivolumab

Placebo of Maat013 DRUG

expérimental drug placebo of MaaT013

Also known as: fecal microbiotherapy placebo

fecal microbiotherapy Placebo associated to ipilimumab and nivolumab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18 to 80
• Patients with unresectable or metastatic melanoma
• Patients with ECOG performance of 0-2
• Patients able to provide written informed consent and understand the risks associated with MaaT013
• Have measurable disease as per RECIST version 1.1, on a tumor evaluation (either CT scan, physical evaluation or ultrasonography) performed less than 2 weeks before screening visit
• Requiring a treatment with Ipilimumab and PD1 inhibitor (Nivolumab) and having no contraindication to these drugs nor to their excipients
• Patients unexposed to ipilimumab and anti PD1 or anti PDL1 except if they have received it in the adjuvant setting (if the last dose of Ipilimumab® or anti PD1 or anti PDL1 was received at least 6 months before randomization).
• Negative pregnancy test (serum)
• Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab, ipilimumab and 6 months after the last dose of study treatment (ie, 30 days (duration of ovulatory cycle) plus the time required for the investigational drug to undergo approximately five half-lives)
• Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab, ipilimumab and 7 months after the last dose of study treatment {i.e., 90 days (duration of sperm turnover) plus the time required for the investigational drug to undergo approximately five half-lives.}
• Hemoglobin ≥9 g/dL
• Platelets ≥ 100000mm3
• Neutrophils ≥ 1500/mm3
• Creatinine Clearance ≥ 50mL/mn
• AST ≤ 3N

You may not qualify if:

• Pregnant or breastfeeding women
• Antibiotics in the last two weeks prior to the FMT
• Inability to retain enemas
• Expected to require any other form of systemic or localized anti-neoplastic therapy while on study
• Active infection requiring systemic therapy.
• Active, known or suspected autoimmune disease.
• No health insurance,
• Patients already included in a clinical research other than an observational study (e.g: registry, cohort).
• Patient on AME (state medical aid) (unless exemption from affiliation)
• Patients guardianship/legal protection/curatorship
• Contraindication to fecal transplantation
• Known hypersensitivity to Normacol or Moviprep® or equivalent patent medicines enema or one of their components.
• Fluid-electrolyte disorders with sodium retention (heart failure, hyperaldosteronism, drug-induced edema)
• Recent acute coronary syndrome or unstable ischemic heart disease
• Congestive heart failure ≥ Class III or IV as defined by New York Heart Association

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (5)

Ambroise Paré

Boulogne-Billancourt, Boulogne-Billancourt, 92100, France

Location

Hôpital Lille

Lille, Lille, 44093, France

Location

Hôpital Nantes Hôtel Dieu

Nantes, Nantes, 44000, France

Location

Hôpital Saint Louis

Paris, Paris, 75010, France

Location

Hôpital Gustave Roussy

Villejuif, Villejuif, 94800, France

Location

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab; Nivolumab; MoviPrep; Normacol

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: At week 27, unblinding will be performed on patients who progressed. For those who received Placebo, Maat 013 will be administrated in open label.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multi-center, prospective, randomized, double blinded, pilot, proof-of concept, clinical trial

Study Record Dates

• First Submitted: June 25, 2021
• First Posted: August 4, 2021
• Study Start: January 20, 2022
• Primary Completion: August 30, 2024
• Study Completion: April 22, 2025
• Last Updated: August 28, 2025

Record last verified: 2025-07

Locations

FR (5)