Analysis of the Mechanisms of Actions of Heat Shock Protein (Hsp27) Responsible of the Androgen-independent Evolution in Prostate Cancer

NCT ID: NCT02055846

Last Updated: 2015-06-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2015-06-30

Brief Summary

Prostate cancer (PC) represents one of the most common cancers in industrialized countries. Patients with localized disease may be treated with surgery or radiation, while androgen ablation is used as first-line therapy in patients with metastatic disease. While most patients initially respond well to this hormonal therapy, they most ultimately become unresponsive and recur within 2 years as androgen-independent prostate cancer (AIPC). Recently, docetaxel-based regimens have demonstrated improved survival in men with AIPC in two different, large, phase III studies. However, the median overall survival was prolonged for only 2 or 3 months. Androgen independent (AI) progression involves variable combinations of clonal selection, adaptive up-regulation of anti-apoptotic genes, ligand-independent androgen receptor (AR) activation, alternative growth factor pathways, and immune system escape. Additional therapeutic strategies targeting molecular mechanisms mediating resistance, combined with immunotherapy must be developed. One strategy to improve therapies in advanced PC involves targeting genes that are activated by androgen withdrawal, either to delay or prevent the emergence of the resistant AI phenotype. Recently, a scientist,identified Heat Shock Protein (Hsp27) as a highly over-expressed gene in AIPC. Hsp27 knockdown using antisens oligonucleotides (ASO) and small interfering RNA (siRNA) increased apoptotic rates and enhanced hormone- and chemo-therapy in PC. She developed and patented a 2nd generation ASO targeting Hsp27 that has been licensed (investigational drug called OGX-427) and clinical trials phase I/II is currently in process in PC. Despite OGX-427 efficiency, the functional role of stress induced Hsp27 in castration or chemotherapy-induced apoptosis remains undefined. The purpose of this study is to elucidate the pathways leading to Hsp27 action in androgen-independent prostate cancer in order to 1/ Increase the pharmacological safety of OGX-427 and 2/find new specific therapeutic targets and treatment strategy for androgen-independent prostate cancer .

Conditions

Androgen-independent Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

prostate cancer

Realisation of blood sample, urinary sample and tumor biopsy

Group Type: EXPERIMENTAL

Realisation of blood sample, urinary sample and tumor biopsy

Intervention Type: PROCEDURE

Interventions

Realisation of blood sample, urinary sample and tumor biopsy

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Prostate adenocarcinoma
• Patient > 18 years old
• Patient affiliated to a social security system or benefiting from such a system
• Signed consent to participate

Exclusion Criteria

• Patient in emergency situation, major person being the object of a legal protective measure or unable to express its consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Institut Paoli-Calmettes

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gwénaëlle GRAVIS, MD

Role: PRINCIPAL_INVESTIGATOR

Institut Paoli-Calmettes

Locations

Gwénaëlle GRAVIS, MD

Marseille, , France

Countries

France

Related Links

http://www.institutpaolicalmettes.fr

official web site of the sponsor

Other Identifiers

PPPR / IPC 2012-002

Identifier Type: -

Identifier Source: org_study_id