Immune Profiles Evolution Under Immunotherapy for Melanoma (EPITHEM)

Immune Profiles Evolution in Patients Treated by Immunotherapy for Melanoma

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.

Study Overview

• Status: Recruiting
• Conditions: Melanoma
• Intervention / Treatment: Procedure: venous puncture; Procedure: tumoral biopsy

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elisa FUNCK-BRENTANO, MD; Phone Number: +33 (0)1 71 16 77 21; Email: elisa.funck-brentano@aphp.fr

Study Locations

• France
  • Boulogne-Billancourt, France, 92100
    • Recruiting
    • Dermato-oncology Department, Ambroise Paré Hospital, APHP

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: experimental group	Procedure: venous puncture; 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).; Procedure: tumoral biopsy; Cutaneous biopsy: superficial skin, or extended skin biopsy, if it is indicated for patient's care.
Active Comparator: comparator group	Procedure: venous puncture; 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).; Procedure: tumoral biopsy; Cutaneous biopsy: superficial skin, or extended skin biopsy, if it is indicated for patient's care.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Elisa FUNCK-BRENTANO, MD, Dermato-oncology Department, Ambroise Paré Hospital, APHP; Study Director: Jean-François EMILE, MD, PhD, Pathology department, Ambroise Paré hospital, APHP

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2021
• Primary Completion (Estimated): January 1, 2031
• Study Completion (Estimated): January 1, 2031

Study Registration Dates

• First Submitted: September 14, 2020
• First Submitted That Met QC Criteria: October 5, 2020
• First Posted (Actual): October 6, 2020

Study Record Updates

• Last Update Posted (Actual): April 6, 2025
• Last Update Submitted That Met QC Criteria: April 4, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: immunotherapy; melanoma; immune profiles
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma
• Other Study ID Numbers: APHP200947; 2019-A02695-52 (Registry Identifier: IDRCB)

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