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

June 24, 2015 updated by: Institut Paoli-Calmettes

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

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 .

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

59

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Marseille, France, 13009
        • Gwénaëlle GRAVIS, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: prostate cancer
Realisation of blood sample, urinary sample and tumor biopsy
Procedure: Realisation of blood sample, urinary sample and tumor biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Level of Hsp27 protein
Time Frame: within 24 hours
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Targets for OGX-427
Time Frame: within 24 hours
Description of new specific therapeutic targets for androgen-independent prostate cancer and pharmacological safety of OGX-427
within 24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut Paoli-Calmettes

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2012

Primary Completion (ACTUAL)

June 1, 2015

Study Completion (ACTUAL)

June 1, 2015

Study Registration Dates

First Submitted

October 26, 2012

First Submitted That Met QC Criteria

February 4, 2014

First Posted (ESTIMATE)

February 5, 2014

Study Record Updates

Last Update Posted (ESTIMATE)

June 25, 2015

Last Update Submitted That Met QC Criteria

June 24, 2015

Last Verified

December 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PPPR / IPC 2012-002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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