melonoma MedDRA version: 21.1 Level: LLT Classification code 10053571 Term: Melanoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: MaaT013
Product Code: 7P010
Pharmaceutical Form: Rectal solution
INN or Proposed INN: MaaT013 - 7P010
Current Sponsor code: MaaT013 - 7P010
Other descriptive name: ALLOGENEIC FAECAL MICR
Sponsors
Assistance Publique - Hôpitaux de Paris (AP-HP)
Eligibility
Sex/Gender
All
Inclusion 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 =65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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;Secondary Objective: - To assess whether a 23-week treatment with MaaT013, combined with Ipilimumab and Nivolumab, is more efficient than Ipilimumab and Nivolumab + placebo - To assess changes in the tumor microenvironment in patients who have received MaaT013 and placebo ; - 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 -To assess peripheral blood T cell subpopulations that have been identified as associated with gut microbiome composition or response to anti CTLA-4 and anti PD1 in previous human studies; - To assess the evolution of gut microbial members and metabolites; - To assess, on an open basis, the efficacy and safety of MaaT013 combined with Nivolumab in a subset of patients who failed to respond to placebo+Ipilimumab and Nivolumab in the randomized part of the trial. ;Primary end point(s): Safety will be measured by the occurrence of Grade 3 and grade 4 adverse events (AE), as graded by the CTCAE v 5.0 during the 27 weeks of the trial. ;Timepoint(s) of evaluation of this end point: Week 27 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Efficacy will be assessed by the best overall response rate, rated by immunological Response Evaluation Criteria in Solid Tumors (iRECIST; 19) in the experimental and control arms and among them, within the subgroup of patients who carried the unfavourable baseline microbiota. - Changes in the tumor micro environment (TME) pre and post MaaT013 or placebo - 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 - Changes in peripheral blood immune cell subpopulations pre and post MaaT013 or placebo - Changes in gut microbiome and metabolites pre and post MaaT013 or placebo - Overall response rate, either complete or partial, rated by RECIST in patients with a stable disease or disease progression who received placebo and subsequently, MaaT013, in an open-label basis. - Progression-free survival at week 15, 27, 51 - Overall survival at week 15, 27, 51 - Best overall response rate, either complete or partial, rated by RECIST v1.1. and PET scan - Disease control rate (complete or partial response or stable disease) - Pseudo progression rate ;Timepoint(s) of evaluation of this end point: until Week 51 | — |
Countries
France
Contacts
Public ContactDRCI - Hôpital Saint Louis
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS
Outcome results
None listed