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

NCT05649683 | Recruiting

• 1 other identifier: 22-PP-14
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

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)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Evaluation of predictifve Th1, Th2 and Th17 cytokine production correlate to the progression free

  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

  Change from Baseline immunological toxicity occurrence at week 6 and at week 11

Study Arms (1)

Analysis of blood cytokine

OTHER

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

Interventions

Evaluation of cytokine production 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

Analysis of blood cytokine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nice: lead

Study Sites (3)

CHU de Nice - Hôpital de l'Archet

Nice, Alpes-maritimes, 06200, France

RECRUITING

CHU de Montpellier

Montpellier, Occitanie, 34285, France

RECRUITING

CHRU de Lille

Lille, 59000, France

NOT YET RECRUITING

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Montaudie Henri, PhD

  CHU de Nice, Service de Dermatologie

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Montaudie Henri, PhD

CONTACT

33492036083; montaudie.h@chu-nice.fr

Pradelli Emmanuelle

CONTACT

33492036083; pradelli.e@chu-nice.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2022
• First Posted: December 14, 2022
• Study Start: January 31, 2023
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: June 4, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)