Study of Alterations in Tumor Metabolism Associated With the Development of Immunotherapy Resistance in Melanoma (MEL-META)

Among the mechanisms responsible for resistance to immunotherapy, metabolism seems to play a major role. A better understanding of tumor metabolism appears to be absolutely necessary in order to propose efficient therapeutic alternatives to target tumor cells without exerting a deleterious effect on the cells responsible for the anti-tumor immune response. The main objective is to evaluate metabolism modulations in melanoma cells extracted from metastases of patients sensitive and resistant to immunotherapies (anti-PD1 or anti-PD1+anti-CTLA4).

Study Overview

• Status: Recruiting
• Conditions: Melanoma (Skin)
• Intervention / Treatment: Other: Biposy

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Montaudie Henri; Phone Number: +33492036488; Email: montaudie.h@chu-nice.fr

Study Locations

• France
  • Alpes-maritimes
    • Nice, Alpes-maritimes, France, 06001
      • Recruiting
      • CHU de Nice
      • Contact: Montaudie Henri; Email: montaudie.h@chu-nice.fr
      • Principal Investigator: Montaudie Henri

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Female or male, 18 years of age or older
• Stage III unresectable or histologically confirmed stage IV cutaneous melanoma (melanoma of unknown origin is accepted), treatment naïve (metastatic stage) and for which immunotherapy will be started
• Performance Status ≤1
• BRAF status available; BRAF status determination is required but patient will be eligible regardless of BRAF status
• For women of childbearing potential, effective contraception must be initiated during the study.
• Patient affiliated to social security plan
• Patient having signed informed consent

Exclusion Criteria:

• Breastfeeding or pregnant patients: for women of childbearing age, a urine pregnancy test will be performed
• Patients with ocular or mucosal melanoma of metastatic ocular melanoma
• Patients with metastatic melanoma not treated with immunotherapy (i.e. treated with a combination of targeted therapies).
• Contraindication to the initiation of immunotherapy: HIV and/or HCV and/or HBV positive, active autoimmune disease (chronic inflammatory bowel disease such as ulcerative colitis, Crohn's disease, vasculitis, etc.), patients with autoimmune motor neuropathy (such as Guillain Barré syndrome).
• Vulnerable patients: minors, adults under guardianship or curatorship, deprived of liberty
• Vulnerable persons (minors, patients under guardianship or curatorship, deprived of liberty, under court protection, etc.).
• A psychiatric or addiction history that will compromise the patient's ability to consent and follow the proper protocol procedures
• Any other clinical finding that, in the opinion of the principal investigator, could interfere with the results of the study or pose a risk to the patient during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• 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: melanoma inclusion; Biopsy of a metastasis allowing melanoma diagnosis and realization of primary cultures for metabolomics. An additional 20ml blood sample will also be taken to quantify circulating metabolites and to isolate PBMC.	Other: Biposy; Biopsy at inclusion visit and at disease progression if applicable

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline pyrimidine metabolism at 4 years	Investigation of modulations of pyrimidine metabolism using isotopically labelled glutamine	At inclusion visit and 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival (OS) will be measured using the Kaplan-Meier method	At inclusion visit and 4 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2022
• Primary Completion (Estimated): May 25, 2028
• Study Completion (Estimated): October 25, 2028

Study Registration Dates

• First Submitted: March 10, 2022
• First Submitted That Met QC Criteria: March 31, 2022
• First Posted (Actual): April 1, 2022

Study Record Updates

• Last Update Posted (Actual): September 6, 2023
• Last Update Submitted That Met QC Criteria: September 5, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: 21-PP-20

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