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

Androgen-independent Prostate Cancer Clinical Trial

Official title:

Analysis of the Mechanisms of Actions of Hsp27 Responsible of the Androgen-independent Evolution in Prostate Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02055846
• Other study ID #: PPPR / IPC 2012-002
• Status: Terminated
• Phase: N/A
• First received: October 26, 2012
• Last updated: June 24, 2015
• Start date: March 2012
• Est. completion date: June 2015

Study information

• Verified date: December 2012
• Source: Institut Paoli-Calmettes
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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 .

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 59
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Androgen-independent Prostate Cancer
• Prostatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
France	Gwénaëlle GRAVIS, MD	Marseille

Sponsors (1)

Lead Sponsor	Collaborator
Institut Paoli-Calmettes

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Targets for OGX-427	Description of new specific therapeutic targets for androgen-independent prostate cancer and pharmacological safety of OGX-427	within 24 hours	No

External Links

•   official web site of the sponsor