Ignite Creation Date:
2025-12-24 @ 11:48 PM
Ignite Modification Date:
2026-02-27 @ 10:38 AM
Study NCT ID:
NCT02310451
Status:
COMPLETED
Last Update Posted:
2023-09-08
First Post:
2014-11-13
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Study of Molecular Mechanisms Implicated in the Pathogenesis of Melanoma. Role of Exosomes
Sponsor:
Centre Hospitalier Universitaire de Nice
Organization:
Study Overview
Official Title:
Pilot Study of Exosomes Before and After BRAF Inhibitor Therapy in Patients With Advanced Unresectable or Metastatic BRAF Mutation-positive Melanoma
Status:
COMPLETED
Status Verified Date:
2023-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
EXOSOMES
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.
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.
Detailed Description:
Metastatic melanoma is an aggressive tumor with a 5-year survival rate of about 6 months. Although recent progresses have been made in the treatment of metastatic melanoma, 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 current treatments and / or to discover new anti-metastatic melanoma treatments.
Drugs such as the alkylating agents (temozolomide and fotemustine) or vemurafenib trigger senescence-like phenotypes in melanoma cells. Although senescence is a process that limits the proliferation of cells, it is now known that senescent cells secrete factors that exert a pro-tumoral role. If many studies have focused on the role of the soluble factors of this secretome, 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. The exovesicules discharged by a cell in its environment are the subject of increasing interest in oncology as a prognostic factor and marker of therapeutic response. Several studies showed that these vesicles shape the tumor microenvironment and contribute to the migration of cancer cells.
This 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 production, quantity, size and composition of 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.
Drugs such as the alkylating agents (temozolomide and fotemustine) or vemurafenib trigger senescence-like phenotypes in melanoma cells. Although senescence is a process that limits the proliferation of cells, it is now known that senescent cells secrete factors that exert a pro-tumoral role. If many studies have focused on the role of the soluble factors of this secretome, 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. The exovesicules discharged by a cell in its environment are the subject of increasing interest in oncology as a prognostic factor and marker of therapeutic response. Several studies showed that these vesicles shape the tumor microenvironment and contribute to the migration of cancer cells.
This 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 production, quantity, size and composition of 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.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: