Immunological Functionnal Test Validation to Predict Melanoma Metastatic Patient Response to Checkpoint Inhibitors (mela-quantif)

Immunological Functionnal Test Validation to Predict Melanoma Metastatic Patient Response to Checkpoint Inhibitors - Melanoma Quantiferon

Checkpoint inhibitor such as anti-CTLA-4 and anti-PD-1 are known to block inhibitory signals and increase the immune antimutoral response. Nivolumab and Ipilimumab association is considered as a more efficient immunotherapy to treat advanced melanoma. This combined immunotherapy is also responsible of severe immunes toxicyties. Identification of predictives biomarqueurs remains a challenge to predict the balance between tolerability and efficency. Previous data showed that advanced melanoma patient had lower level of Th1 cytokines that predict a less efficient immune system than healthy donors. The second point was that high level of Th1 and Th17 cytokines were correlate to a better tumor response. The last point was that patients with severe immune toxicity showed an increase of IL-6 and IL17a production. The investigators would like to identify the predictive values of Th1, Th2 and Th17 at the begining and during the combined immunotherapy and correlate these cytokines levels secretions to a potential efficient tumor response or to the emergence of induced immunes toxicities. This study is an original approach using functionnal test to predict the balance between efficienty and tolerability.

Study Overview

• Status: Recruiting
• Conditions: Melanoma (Skin)
• Intervention / Treatment: Biological: Evaluation of cytokine production

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Montaudie Henri, PhD; Phone Number: 33492036083; Email: montaudie.h@chu-nice.fr
• Study Contact Backup: Name: Pradelli Emmanuelle; Phone Number: 33492036083; Email: pradelli.e@chu-nice.fr

Study Locations

• France
  • Lille, France, 59000
    • Not yet recruiting
    • CHRU de Lille
    • Contact: Mortier Laurent, PhD; Phone Number: 0033320444193; Email: laurent.mortier@chru-lille.fr
    • Sub-Investigator: Mortier Laurent, PhD
  • Alpes-maritimes
    • Nice, Alpes-maritimes, France, 06200
      • Recruiting
      • CHU de Nice - Hôpital de l'Archet
      • Contact: Montaudie Henri, PhD; Phone Number: 33492036083; Email: montaudie.h@chu-nice.fr
      • Contact: Seitz Barbara, PhD; Email: seitz.b@chu-nice.fr
      • Principal Investigator: montaudie Henri, PhD
  • Occitanie
    • Montpellier, Occitanie, France, 34285
      • Recruiting
      • CHU de Montpellier
      • Contact: Dereure Olivier, PhD; Phone Number: 33467336906; Email: o-dereure@chu-montpellier.fr
      • Sub-Investigator: Dereure Olivier, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion

• persone of major age,
• advanced melanoma confirmed,
• RECIST 1.1 disease,
• first line treatment

Exclusion Criteria:

• occular and mucosal melanoma,
• previous checkpoint inhibitor treatment,
• active brain metastasis,
• concomitant immunosuppressive treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Analysis of blood cytokine; Patients will receive anti-PD1 therapy (Nivolumab/Nivo) with anti-CTLA4 therapy (Ipilimumab/Ipi) as part of routine care, as per the MA scheme followed in case of efficacy and good tolerance of Nivolumab maintenance treatment alone. The functional test for cytokines (1ml total blood on lihtium heparinate) will be performed at the initiation of ICI (J0), at week 6 (S6, after the 2nd cure), at week 11 (S11= 1st radiological evaluation, after the 4 cures of Nivo+Ipi), and, if applicable, the progression of the disease and/or the occurrence of an ESi grade 3-4. Stimulated lymphocytes from non-therapy responders will be tested in vitro by various immunomodulatory drugs. During each sampling we will also collect 5 ml of serum on dry tube for serological constitution, 3ml on EDTA tube for performing an immunophenotyping (T, B, NK) and 3ml on EDTA tube for freezing total PBMC and setting up a biobank.

Biological: Evaluation of cytokine production; The patient will have samples at initiation of treatment (J0), after treatments 1 and 2 (S6), after the first radiological assessment at S11 and/or the progression of the disease and/or occurrence of a grade 3-4 adverse event

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of predictifve Th1, Th2 and Th17 cytokine production correlate to the RECIST 1.1 tumoral response	Analysis of blood cytokine secretion upon non specific in vitro stimulation RECIST 1.1 tumor response	Change from Baseline tumoral response at week 6 and at week 11

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of predictifve Th1, Th2 and Th17 cytokine production correlate to the progression free	Analysis of blood cytokine secretion upon non specific in vitro stimulation disease progression	Change from Baseline disease progression at week 6 and at week 11
Evaluation of predictifve Th1, Th2 and Th17 cytokine production correlate to severe immunological toxicity occurrence	Analysis of blood cytokine secretion upon non specific in vitro stimulation severe immunological toxicity occurrence	Change from Baseline immunological toxicity occurrence at week 6 and at week 11

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice
• Investigators: Principal Investigator: Montaudie Henri, PhD, CHU de Nice, Service de Dermatologie

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2023
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: November 24, 2022
• First Submitted That Met QC Criteria: December 5, 2022
• First Posted (Actual): December 14, 2022

Study Record Updates

• Last Update Posted (Estimated): June 4, 2024
• Last Update Submitted That Met QC Criteria: June 3, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma
• Other Study ID Numbers: 22-PP-14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No