Using fecal microbiome transfer to enhance melanoma treatment
Prospective randomIzed Clinical Trial Assessing the Tolerance and Clinical Benefit of feCAl tranSplantation in patientS With melanOma Treated With CTLA-4 and PD1 Inhibitors
This study is testing whether a treatment that transfers healthy gut bacteria can help people with advanced melanoma respond better to immunotherapy drugs.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 60 (estimated) |
| Ages | 18 Years to 80 Years |
| Sex | All |
| Sponsor | Assistance Publique - Hôpitaux de Paris Academic / other |
| Drugs / interventions | Ipilimumab, Nivolumab, immunotherapy |
| Locations | 3 sites (Nantes and 2 other locations) |
| Trial ID | NCT04988841 on ClinicalTrials.gov |
What this trial studies
This clinical trial investigates the effects of fecal microbiome transfer (FMT) using a standardized product called MaaT013 in patients with unresectable or metastatic melanoma. The study aims to determine if FMT can improve the response to immunotherapy treatments, specifically ipilimumab and nivolumab, by altering the gut microbiome composition. It is a randomized, proof-of-concept trial involving 60 patients who have not previously been treated with these immunotherapies. Participants will receive either the FMT or a placebo alongside their immunotherapy regimen, with evaluations conducted throughout the study period.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 to 80 with unresectable or metastatic melanoma who have not previously been treated with ipilimumab or anti-PD1 therapies.
Not a fit: Patients who have previously received ipilimumab or anti-PD1 therapies within the last six months may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could significantly enhance the effectiveness of immunotherapy in melanoma patients.
How similar studies have performed: While this approach is novel in the context of melanoma treatment, previous studies have shown promising results with fecal microbiome transfer in other cancer types.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
* 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
* ALT ≤ 3N
* Total bilirubin ≤ 1.5N (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)
* Alkaline phosphatase ≤ 3N
* INR \< 1.5
* Prothrombin ≥ 70%
* TCA \< 1.2
* No Hepatocellular insufficiency
Exclusion Criteria:
* 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
* Hypersensitivity to the active substances or to any of the excipients: Aspartame (E951), Acesulfame, potassium (E950), lemon flavor (maltodextrin, citral, lemon essential oil, lime essential oil, xanthan gum, vitamin E)
* Gastrointestinal obstruction or perforation
* Gastric emptying disorders (gastroparesis),
* Ileus,
* Phenylketonuria (due to the presence of aspartame),
* Deficiency in glucose-6-phosphate dehydrogenase (due to the presence of ascorbate),
* Toxic megacolon, in severe forms of inflammation of the intestinal tract, including Crohn's disease and ulcerative colitis.
Where this trial is running
Nantes and 2 other locations
- Hôpital Nantes Hôtel Dieu — Nantes, France (Recruiting)
- Hôpital Saint Louis — Paris, France (Recruiting)
- Hôpital Gustave Roussy — Villejuif, France (Recruiting)
Study contacts
- Study coordinator: Franck CF CARBONNEL, Professor
- Email: Franck.carbonnel@aphp.fr
- Phone: + (33) 145213722
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.