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

NCT ID: NCT05649683

Last Updated: 2024-06-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-31
• Study Completion Date: 2027-06-01

Brief Summary

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.

Conditions

Melanoma (Skin)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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.

Group Type: OTHER

Evaluation of cytokine production

Intervention Type: BIOLOGICAL

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

Interventions

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire de Nice

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Montaudie Henri, PhD

Role: PRINCIPAL_INVESTIGATOR

CHU de Nice, Service de Dermatologie

Locations

CHU de Nice - Hôpital de l'Archet

Nice, Alpes-maritimes, France

Site Status: RECRUITING

CHU de Montpellier

Montpellier, Occitanie, France

Site Status: RECRUITING

CHRU de Lille

Lille, , France

Site Status: NOT_YET_RECRUITING

Countries

France

Central Contacts

Montaudie Henri, PhD

Role: CONTACT

montaudie.h@chu-nice.fr

33492036083

Pradelli Emmanuelle

Role: CONTACT

pradelli.e@chu-nice.fr

33492036083

Facility Contacts

Montaudie Henri, PhD

Role: primary

montaudie.h@chu-nice.fr

33492036083

Seitz Barbara, PhD

Role: backup

seitz.b@chu-nice.fr

Dereure Olivier, PhD

Role: primary

o-dereure@chu-montpellier.fr

33467336906

Mortier Laurent, PhD

Role: primary

laurent.mortier@chru-lille.fr

0033320444193

Other Identifiers

22-PP-14

Identifier Type: -

Identifier Source: org_study_id