Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02310451
Recruitment Status : Unknown
Verified March 2016 by Centre Hospitalier Universitaire de Nice.
Recruitment status was:  Recruiting
First Posted : December 8, 2014
Last Update Posted : March 22, 2016
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nice

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.


Condition or disease Intervention/treatment Phase
Metastatic Melanoma Biological: blood test Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: Pilot Study of Exosomes Before and After BRAF Inhibitor Therapy in Patients With Advanced Unresectable or Metastatic BRAF Mutation-positive Melanoma
Study Start Date : December 2014
Actual Primary Completion Date : December 2015
Estimated Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: metastatic melanoma
Patients affected by advanced melanoma not resectable (stage IIIc) or metastatic (stage IV)
Biological: blood test
blood test to J0-M3-M6-M12




Primary Outcome Measures :
  1. number of exosomes [ Time Frame: change from Day 0 at Month12 ]
    Measure of the number of exosomes (µg of proteins or particles)/ml in peripheral blood by differential ultracentrifugation before and after treatment.


Secondary Outcome Measures :
  1. number of patient with a detection test of exosomes positive measured [ Time Frame: change from Day 0 at Month12 ]
    Calculation of number of patients with a detection test of exosomes positive measured in the peripheral blood after differential ultracentrifugation by protein assay and Nanosight before and after treatment.

  2. survival [ Time Frame: Month 12 ]
    Difference in survival (overall survival and progression frre-survival) between patients depending on the size and number of exosomes (µg of proteins or particles)/ml before and after treatment, according to the method of Kaplan Meier

  3. Tumoral response [ Time Frame: Month 12 ]
    Difference of tumoral response (RECIST criteria) between patients depending on variation of the number of exosomes (µg of proteins or particles)/ml, size and composition before and after treatment.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02310451


Contacts
Layout table for location contacts
Contact: Henri MONTAUDIE, PH montaudie.h@chu-nice.fr
Contact: Vanina OLIVERI, CRA 0033 4 92 03 42 54 oliveri.v@chu-nice.fr

Locations
Layout table for location information
France
CHU de Nice ^Hôpital de l'Archet Recruiting
Nice, France, 06200
Contact: Vanina OLIVERI, CRA    0033 4 92 03 42 54    oliveri.v@chu-nice.fr   
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nice
Investigators
Layout table for investigator information
Principal Investigator: Henri MONTAUDIE, PH Centre Hospitalier Universitaire de Nice
Layout table for additonal information
Responsible Party: Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier: NCT02310451    
Other Study ID Numbers: 14-AOI-10
First Posted: December 8, 2014    Key Record Dates
Last Update Posted: March 22, 2016
Last Verified: March 2016
Additional relevant MeSH terms:
Layout table for MeSH terms
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas