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

NCT02055846 | Terminated

• 1 other identifier: PPPR / IPC 2012-002
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

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

Keywords

Androgen-independent prostate cancer

Outcome Measures

Primary Outcomes (1)

• Level of Hsp27 protein

  Mechanisms of action of Hsp27 protein to elucidate the pathways leading to Hsp27 action in androgen-independent prostate cancer (AIPC) by double hybrid Sos Recruitment System (SRS)

  within 24 hours

Secondary Outcomes (1)

• Targets for OGX-427

  within 24 hours

Study Arms (1)

prostate cancer

EXPERIMENTAL

Realisation of blood sample, urinary sample and tumor biopsy

Procedure: Realisation of blood sample, urinary sample and tumor biopsy

Interventions

Realisation of blood sample, urinary sample and tumor biopsy PROCEDURE

prostate cancer

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Institut Paoli-Calmettes: lead

Study Sites (1)

Gwénaëlle GRAVIS, MD

Marseille, 13009, France

Location

Related Links

• official web site of the sponsor

Study Officials

• Gwénaëlle GRAVIS, MD

  Institut Paoli-Calmettes

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 26, 2012
• First Posted: February 5, 2014
• Study Start: March 1, 2012
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: June 25, 2015

Record last verified: 2012-12

Locations

FR (1)