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MelanomaPhase 2PICASSONCT04988841

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

A Phase 2 study testing MaaT013, Ipilimumab and Nivolumab in people with Melanoma, run by Assistance Publique - Hôpitaux de Paris at 5 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Melanoma
What is being tested?
MaaT013, Ipilimumab and Nivolumab
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
70 participants
Where
5 sitesFrance
Study dates
20 Jan 2022to 22 Apr 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

France5 sites

  • Ambroise Paré

    Boulogne-Billancourt, Boulogne-Billancourt, 92100

  • Hôpital Lille

    Lille, Lille, 44093

  • Hôpital Nantes Hôtel Dieu

    Nantes, Nantes, 44000

  • Hôpital Saint Louis

    Paris, Paris, 75010

  • Hôpital Gustave Roussy

    Villejuif, Villejuif, 94800

Other trials in France

About this study

Official title: Prospective randomIzed Clinical Trial Assessing the Tolerance and Clinical Benefit of feCAl tranSplantation in patientS With melanOma Treated With CTLA-4 and PD1 Inhibitors

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.

Read the detailed description

PICASSO is a prospective, randomized, proof of concept clinical trial. This trial is about assessing the tolerance and clinical benefit of fecal microbiome transfer in patients with melanoma in addition to the usual treatment with immunotherapy combining ipilimumab (CTLA-4 inhibitor) and nivolumab (PD-1 inhibitor).

In the proposed research, we will compare faecal transplantation using MaaT013 to placebo in 70 patients.

Patients not exposed to anti CTLA-4 and anti PD1 or PDL-1 patients before the trial will be randomized to receive either: ipilimumab + nivolumab + MaaT013 (n = 35) or ipilimumab + nivolumab + placebo (n = 35).

The estimated duration of the study is 37 months. Administration of MaaT013 or placebo will be performed every 3 weeks between baseline and week 9 then from week 15 to week 23 every 4 weeks. A total of 7 fecal microbiome transfer will be performed.

Prior to the first administration (the day before) an evacuating enema by (MOVIPREP or equivalent) will be done, For subsequent administrations, an evacuating enema (equivalent to the specialty Normacol®) will be administered rectally before the transplantation of fecal microbiota or the placebo.

Blood and stool samples will be collected as well as biopsies for the purposes of the study.

An evaluation of the patient's condition will be made at week 27, Unblinding will be performed for patients who have progressed. Patients with disease progression who received placebo will be considered for receiving MaaT013, in an open-label basis, concurrently with nivolumab infusions, at week 31, 35, 39, 43 and 47.

. The end-of-follow-up visit for all patients is scheduled for week 51. Patients who met the inclusion criteria, received Ipilimumab+Nivolumab, who consented to have a baseline stool microbiota analysis before starting treatment with ipilimumab + nivolumab. They will form a cohort of 50 patients.

Conditions
Melanoma
Being tested
MaaT013, Ipilimumab, Nivolumab, MoviPrep, Normacol
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
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MaaT013Drug

    Also called fecal microbiotherapy

    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)

  • IpilimumabDrug

    Anti cytotoxicT-lymphocyte-associated protein 4 ( immunothérapy)

  • NivolumabDrug

    AntiPD1 ( immunothérapy)

  • MoviPrepDrug

    Also called Osmotic laxative solution

    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)

  • NormacolDrug

    Also called hypertonic enema solution

    hypertonic enema solution

  • Placebo of Maat013Drug

    Also called fecal microbiotherapy placebo

    expérimental drug placebo of MaaT013

Study groups in NCT04988841
Study groupRoleWhat they receive
Fecal microbiotherapy (MaaT013) associated to ipilimumab and nivolumabExperimentalFecal 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
Receives: Drug: MaaT013; Drug: Ipilimumab; Drug: Nivolumab; Drug: MoviPrep; Drug: Normacol
fecal microbiotherapy Placebo associated to ipilimumab and nivolumabPlacebo comparatorPlacebo 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
Receives: Drug: MaaT013; Drug: Ipilimumab; Drug: Nivolumab; Drug: MoviPrep; Drug: Normacol; Drug: Placebo of Maat013

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: During the 27 weeks of the trial.

Secondary outcomes (14)

  1. 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.

    Efficacy will be assessed by the best overall response rate, between baseline and week 27, without confirmation of partial or complete response rated by Response Evaluation Criteria in Solid Tumors (RECIST v1.1.; 19) in the experimental and control arms.

    Measured: During the 27 weeks of the trial.

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

    Changes in the tumor micro environment (TME) pre and post MaaT013 or placebo

    Measured: During the 27 weeks of the trial.

  3. 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 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 : IL-6, IL-8, MCP1, IL-1β, TNF α, sCD25, sCTLA-4, sPD-L1, short chain fatty acids (SCFA), all in micromol/L

    Measured: During the 27 weeks of the trial.

  4. 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.

    Changes in peripheral blood immune cell subpopulations pre and post MaaT013 or placebo

    Measured: During the 27 weeks of the trial.

  5. To assess the evolution of gut microbial members and metabolites;

    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.

    Measured: During the baseline and 9 weeks of the trial.

  6. 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

    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

    Measured: During the 51 weeks of the trial.

  7. To assess progression-free survival at week 15, 27, 51

    Progression-free survival rated by RECIST and iRECIST at week 15, 27 and 51

    Measured: During the 15, 27 and 51 weeks of the trial.

  8. To assess response (either partial or complete), stable disease and progression at week 15, 27, 51

    Measured: During the 15, 27 and 51 weeks of the trial.

  9. To assess overall survival at week 15, 27, 51.

    Time point assessment of response (either partial or complete), stable disease and progression at week 15, 27 and 51

    Measured: During the 15, 27 and 51 weeks of the trial.

  10. To assess best overall response rate, either complete or partial, with or without confirmation of response, rated by iRECIST v1.1 and PET scan at weeks 15, 27 and 51, using EORTC criteria

    Best overall response rate, either complete or partial, with or without confirmation of response, rated by iRECIST v1.1. (20) and PET scan at weeks 15, 27 and 51, using EORTC criteria

    Measured: During the 15, 27 and 51 weeks of the trial.

  11. Best overall response rate, with confirmation of response, rated by RECIST (19)

    Best overall response rate, without confirmation of response between baseline and week 27, rated by RECIST (19)

    Measured: During the 27 weeks of the trial.

  12. To assess disease control rate (complete or partial response or stable disease)

    Disease control rate (complete or partial response or stable disease) rated by RECIST and iRECIST

    Measured: During the 15, 27 and 51 weeks of the trial.

  13. To assess pseudo progression rate

    Pseudo progression rate evaluated by iRECIST

    Measured: During the 15, 27 and 51 weeks of the trial.

  14. The description of favorable gut microbiome will be based upon analyses performed in patients of the placebo arm,

    This is why patients who met the inclusion criteria, received Ipilimumab+Nivolumab, who consented to have gut microbiome analyses at baseline and week 9, but were not included in the randomized trial, will be followed until week 27.

    Measured: During the 27 weeks of the trial.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Aug 2021
  2. Study start20 Jan 2022
  3. Primary completion30 Aug 2024
  4. Study completion22 Apr 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Multi-center, prospective, randomized, double blinded, pilot, proof-of concept, clinical trial
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
70 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04988841
Sponsor's protocol ID
APHP200133
Acronym
PICASSO
Status last verified
Jul 2025
First submitted
25 Jun 2021
Last updated
28 Aug 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MaaT013, Ipilimumab and Nivolumab in people with Melanoma, run by Assistance Publique - Hôpitaux de Paris at 5 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: During the 27 weeks of the trial.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04988841.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2025.

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