PICASSO. Prospective randomIzed clinical trial assessing the tolerance and clinical benefit of feCAl tranSplantation in patientS with melanOma treated with CTLA-4 and PD-1 inhibitors
- Conditions
- Melanoma
- Registration Number
- 2024-516100-42-00
- Lead Sponsor
- Assistance Publique Hopitaux De Paris
- Brief Summary
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised, recruitment pending
- Sex
- Not specified
- Target Recruitment
- 70
Patients aged 18 to 80
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 ≥ 100000/mm3
Neutrophils ≥ 1500/mm3
Creatinine Clearance ≥ 50mL/mn
AST ≤ 3N (< 5x ULN in case of liver metastases
ALT ≤ 3N (< 5x ULN in case of liver metastases)
Total bilirubin ≤ 1.5N (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
Alkaline phosphatase ≤ 3N
Patients with unresectable or metastatic melanoma
INR < 1.5 (or within the therapeutic range in patients treated with anticoagulants)
Prothrombin ≥ 70% (or within the therapeutic range in patients treated with anticoagulants)
TCA < 1.2 (or within the therapeutic range in patients treated with anticoagulants
No Hepatocellular insufficiency
Patients with ECOG performance of 0-2
Patients able to provide written informed consent
Patients able to 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)
Pregnant or breastfeeding women
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)
Antibiotics in the last two weeks prior to the FMT
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
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
Patients with a negative Epstein-Barr virus result
Active, known or suspected autoimmune disease.except vitiligo and controlled complemented endocrine autoimmune disease
No health insurance
Patients already included in a clinical research other than an observational study (e.g: registry, cohort)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 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
- Secondary Outcome Measures
Name Time Method Efficacy will be assessed by the best overall response rate, with confirmation of complete or partial response, rated by Response Evaluation Criteria in Solid Tumors (RECIST v1.1; 19) in the experimental and control arms Efficacy will be assessed by the best overall response rate, with confirmation of complete or partial response, rated by Response Evaluation Criteria in Solid Tumors (RECIST v1.1; 19) in the experimental and control arms
Changes in the tumor micro environment (CD3, CD8, FoxP3, CD56, granzyme B, CD68, CD163, CD20, PD1) pre and post MaaT013 or placebo Changes in the tumor micro environment (CD3, CD8, FoxP3, CD56, granzyme B, CD68, CD163, CD20, PD1) 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 ipilimumab + nivolumab with 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 ipilimumab + nivolumab with MaaT013 or placebo
Changes in peripheral blood immune cell subpopulations pre and post ipilimumab + nivolumab with MaaT013 or placebo Changes in peripheral blood immune cell subpopulations pre and post ipilimumab + nivolumab with MaaT013 or placebo
Changes in gut microbiome and metabolites pre and post MaaT013 or placebo and in patients who met the inclusion criteria, received Ipilimumab+Nivolumab, agreed to have stool microbiome analyses at baseline and week 9, but did not receive MaaT013 or placebo Changes in gut microbiome and metabolites pre and post MaaT013 or placebo and in patients who met the inclusion criteria, received Ipilimumab+Nivolumab, agreed to have stool microbiome analyses at baseline and week 9, but did not receive MaaT013 or placebo
Best response rate, either complete or partial, rated by RECIST and iRECIST in patients with disease progression who received placebo and subsequently, MaaT013, in an open-label basis Best response rate, either complete or partial, rated by RECIST and iRECIST in patients with disease progression who received placebo and subsequently, MaaT013, in an open-label basis
Progression-free survival rated by RECIST and iRECIST at week 27, 51 Progression-free survival rated by RECIST and iRECIST at week 27, 51
Overall survival rated by RECIST and iRECIST at week 15, 27, 51 Overall survival rated by RECIST and iRECIST at week 15, 27, 51
Best overall response rate, with or without confirmation of complete or partial response, rated by iRECIST and PET scan at weeks 15, 27 and 51 using EORTC criteria Best overall response rate, with or without confirmation of complete or partial response, rated by iRECIST and PET scan at weeks 15, 27 and 51 using EORTC criteria
Disease control rate (complete or partial response or stable disease) rated by RECIST and iRECIST Disease control rate (complete or partial response or stable disease) rated by RECIST and iRECIST
Pseudo progression rate evaluated by iRECIST Pseudo progression rate evaluated by iRECIST
The favorable gut microbiome is the one associated with the favorable response to ipilimumab and nivolumab. The description of favorable microbiome will be based upon baseline analyses performed in patients of the placebo arm, but also in patients who met the inclusion criteria, received Ipilimumab+Nivolumab, who consented to have a baseline stool microbiota analysis, but were not included in the randomized trial. The favorable gut microbiome is the one associated with the favorable response to ipilimumab and nivolumab. The description of favorable microbiome will be based upon baseline analyses performed in patients of the placebo arm, but also in patients who met the inclusion criteria, received Ipilimumab+Nivolumab, who consented to have a baseline stool microbiota analysis, but were not included in the randomized trial.
Best overall response rate, without confirmation of response, rated by RECIST Best overall response rate, without confirmation of response, rated by RECIST
Trial Locations
- Locations (5)
Hopital Saint Louis
🇫🇷Paris, France
Centre Hospitalier Universitaire De Nantes
🇫🇷Nantes, France
Hopital Ambroise Pare
🇫🇷Boulogne Billancourt, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Centre Hospitalier Universitaire De Lille
🇫🇷Lille, France
Hopital Saint Louis🇫🇷Paris, FranceCéleste LebbéSite contact0142499392celeste.lebbe@aphp.fr