Study of Molecular Mechanisms Implicated in the Pathogenesis of Melanoma. Role of Exosomes

NCT02310451 | Completed

• 1 other identifier: 14-AOI-10
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Recent progresses have been made in the treatment of metastatic melanoma, nevertheless improved patient survival is still limited because of primary resistance and relapses. It is therefore important to continue to understand the molecular mechanisms involved in melanoma development and progression to improve the management of patients. Drugs such as the alkylating agents (temozolomide and fotemustine) or vemurafenib trigger senescence-like phenotypes in melanoma cells. It is now known that senescent cells secrete some factors that exert a pro-tumoral role but the potential existence and the role of insoluble factors remain undetermined. Preliminary results from the investigators laboratory indicate the presence in the senescent secretome of exosomes; microvesicles involved in intercellular communication, immunomodulatory functions, and tumorigenesis. Several studies showed that these vesicles shape the tumor microenvironment and contribute to the migration of cancer cells. Their interest in oncology as a prognostic factor and marker of therapeutic response is increasing. Thus, our project aims to study the effect of exosomes produced by senescent melanoma cells in the development and progression of melanoma in vitro and in vivo using cell cultures and animal models. In addition, the investigator propose a pilot study whose objective is to determine the effect of vemurafenib on nanovesicles produced by patients with advanced unresectable or metastatic melanoma. The investigator hope to show that exosomes participate in the process of drug resistance and relapse, with the goal of developing (with the exosomes study) theranostic tools for personalized care in patients.

Conditions

Metastatic Melanoma

Outcome Measures

Primary Outcomes (1)

• number of exosomes

  Measure of the number of exosomes (µg of proteins or particles)/ml in peripheral blood by differential ultracentrifugation before and after treatment.

  change from Day 0 at Month12

Secondary Outcomes (3)

• number of patient with a detection test of exosomes positive measured

  change from Day 0 at Month12

• survival

  Month 12

• Tumoral response

  Month 12

Study Arms (1)

metastatic melanoma

EXPERIMENTAL

Patients affected by advanced melanoma not resectable (stage IIIc) or metastatic (stage IV)

Biological: blood test

Interventions

blood test BIOLOGICAL

blood test to J0-M3-M6-M12

metastatic melanoma

Eligibility Criteria

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

You may qualify if:

• Subject of both sexes at least 18 years of age
• Patient with advanced melanoma unresectable (stage IIIc) or metastatic (stage IV)
• Patient for whom is considered a systemic treatment by BRAF inhibitor
• Patient no previously treated or no responding to chemotherapy with a last injection\> 1month
• Patient affected by a melanoma measurable according to version 1.1 of RECIST criteria
• Patient with a life expectancy superior than 3 months
• Serum pregnancy test negative for all women of childbearing age
• ECOG ≤1
• Patient affiliated to French social security
• Patient able to understand and communicate with the investigator and to comply with the requirements of the study
• Patient must give a written, signed and dated informed consent before any study related activity is performed. Where relevant, a legal representative will also sign the informed study consent according to local laws and regulations

You may not qualify if:

• Patients not eligible to a BRAF inhibitor therapy or affected by a serious disease wich could require a treatment susceptible to interfere with melanoma treatment
• Pregnant and lactating women
• Patient with active malignancy or a previous malignancy within the past 3 years; except for patient with resected BCC, resected cutaneous SCC, resected carcinoma in-situ of the cervix, and resected carcinoma in-situ of the breast
• Past medical history record of infection with human immunodeficiency virus or viral hepatite C or B
• Any medical or psychiatric condition which, in the Investigator's opinion, would preclude the participant from adhering to the protocol or completing the study per protocol

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nice: lead

Study Sites (1)

CHU de Nice ^Hôpital de l'Archet

Nice, 06200, France

Location

MeSH Terms

Conditions

Melanoma

Interventions

Hematologic Tests

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

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Henri MONTAUDIE, PH

  Centre Hospitalier Universitaire de Nice

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 13, 2014
• First Posted: December 8, 2014
• Study Start: December 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: July 31, 2023
• Last Updated: September 8, 2023

Record last verified: 2023-09

Locations

FR (1)