Immune Profiles Evolution Under Immunotherapy for Melanoma

Study Overview
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Brief Summary
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The primary objective of the study aims to compare the immune profiles (circulating cytokines and lymphocytes) before and after (6 to 8 weeks) the first infusion of immune checkpoint inhibitors in patients with melanoma treated in the adjuvant setting(cohort A) or in metastatic setting(cohort B); and to study the association of these immune profiles with relapse- or progression-free survival.

Detailed Description
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This study will analyse the association of biomarkers with relapse- or progression-free survival of stage III or IV melanoma patients, divided in 3 sub-cohorts: Patients treated in the adjuvant setting (cohort A): new user of immune checkpoint blockers. Patients treated in the metastatic setting (cohort B): - B1: new users of immune checkpoint blockers; - B2: prevalent users of immune checkpoint blockers treated with complementary radiotherapy. For patients of cohort A and B1, immune profiles characteristics will be evaluated before initiation of treatment (=baseline), and at each radiological evaluation of the tumour response, up to maximum 12 months as duration. The maximal duration of treatment will be 12 months for patients treated in the adjuvant setting. For metastatic patients, the duration of treatment will be decided by physician according to different factors (responses, progression, toxicities, ...). For patients in cohort B2, the characteristics of the immune profiles will be evaluated before radiotherapy initiation,, within 6 weeks after the end of radiotherapy, then at the 2 following radiological evaluations of the tumour response

Official Title
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Immune Profiles Evolution in Patients Treated by Immunotherapy for Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Procedure: venous puncture
* Procedure: tumoral biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient aged ≥ 18 years; Totally resected stage III or IV melanoma totally resected, treated with a immune therapy (pembrolizumab or nivolumab ou other immune checkpoint inhibitors) as adjuvant treatment; Unresectable stage IIIC/D or IV metastatic melanoma, treated with immune therapy (pembrolizumab or nivolumab or immune checkpoint inhibitors) which should be associated by a radiotherapy ; Patient has been informed about the study and signed the consent; Affiliated to the French social security scheme. Exclusion Criteria: Pregnant or breastfeeding woman; Patient refusal; Patient receiving a immunosuppressor; Undergo a general corticotherapy of > 10 mg/kg/day since more than 7 days; Patient who participate to another blind interventional study receiving blinded treatment; Patient without any social protection by organization.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experimental group<br> | Procedure: venous puncture<br>* Venous punctures will be performed: for patients of cohort A and B1: before the first immune checkpoint inhibitors monoclonal antibodies infusion (baseline); between week 6 and week 8 (before the immune checkpoint inhibitors monoclonal antibodies infusion); each 3 months up to 12 months. for patients of cohort B2: before the radiotherapy; within the 6 weeks after the end of radiotherapy; at the 2 following evaluations (every 3 months).<br>Procedure: tumoral biopsy<br>* Cutaneous biopsy: superficial skin, or extended skin biopsy, if it is indicated for patient's care.<br>|
| Active Comparator: comparator group<br> | Procedure: venous puncture<br>* Venous punctures will be performed: for patients of cohort A and B1: before the first immune checkpoint inhibitors monoclonal antibodies infusion (baseline); between week 6 and week 8 (before the immune checkpoint inhibitors monoclonal antibodies infusion); each 3 months up to 12 months. for patients of cohort B2: before the radiotherapy; within the 6 weeks after the end of radiotherapy; at the 2 following evaluations (every 3 months).<br>Procedure: tumoral biopsy<br>* Cutaneous biopsy: superficial skin, or extended skin biopsy, if it is indicated for patient's care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of relapse/progression-free survival | Will be noted: all progression and event of death. Survival rate will be calculated between the event's day and the beginning of anticancer treatment. | at 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| immunity profiles | ELISA Multiplex method will be used to analyse inflammatory human cytokines in plasma. This method will performe an assay 45-plex fixed panel : Analytes Included in the Assay CCL2/JE/MCP-1 CCL3/MIP-1 alpha CCL4/MIP-1 beta CCL5/RANTES CCL11/Eotaxin CCL19/MIP-3 beta CCL20/MIP-3 alpha CD40 Ligand/TNFSF5 CX3CL1/Fractalkine CXCL1/GRO alpha/KC/CINC-1 CXCL2/GRO beta/MIP-2/CINC-3 CXCL10/IP-10/CRG-2 EGF FGF basic/FGF2/bFGF Flt-3 Ligand/FLT3L G-CSF GM-CSF Granzyme B IFN-alpha 2/IFNA2 IFN-beta IFN-gamma IL-1 alpha/IL-1F1 IL-1 beta/IL-1F2 IL-1ra/IL-1F3 IL-2 IL-3 IL-4 IL-5 IL-6 IL-7 IL-8/CXCL8 IL-10 IL-12 p70 IL-13 IL-15 IL-17/IL-17A IL-17E/IL-25 IL-33 PD-L1/B7-H1 PDGF-AA PDGF-AB/BB TGF-alpha TNF-alpha TRAIL/TNFSF10 VEGF | quarterly up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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melanoma, immunotherapy, immune profiles