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

Assistance Publique Hopitaux De Paris5 sites in 1 country70 target enrollmentSeptember 27, 2024

DrugsMaaT013 Placebo de MaaT013 - Major ingredients: Calcium carbonate; Xanthan gum; Alimentary colorant; E150d: caramel color; HCl;Purified water

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Not specified
Sponsor: Assistance Publique Hopitaux De Paris
Enrollment: 70
Locations: 5
Primary Endpoint: 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
Status: Not yet recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

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

Registry

euclinicaltrials.eu

Start Date

September 27, 2024

End Date

TBD

Last Updated

last year

Study Type

Interventional clinical trial of medicinal product

Investigators

Sponsor

Assistance Publique Hopitaux De Paris

Responsible Party

Principal Investigator

Franck Carbonnel

Scientific

Assistance Publique Hopitaux De Paris

Eligibility Criteria

Inclusion Criteria

•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)

Exclusion Criteria

•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

Outcomes

Primary Outcomes

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 Outcomes

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 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 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
Progression-free survival rated by RECIST and iRECIST at week 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
Disease control rate (complete or partial response or stable disease) rated by RECIST and 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.
Best overall response rate, without confirmation of response, rated by RECIST