Study on Prolonging Bone Metastasis-Free Survival in Men With Hormone Refractory Prostate Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00286091
First received: February 2, 2006
Last updated: May 20, 2015
Last verified: May 2015
  Purpose

The purpose of this study is to compare the treatment effect of denosumab with placebo on prolonging bone metastasis-free survival in men with hormone refractory (androgen independent) prostate cancer who have no bone metastasis at baseline.


Condition Intervention Phase
Hormone Refractory Prostate Cancer
Biological: Denosumab
Biological: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Phase 3 Study of Denosumab on Prolonging Bone Metastasis-Free Survival in Men With Hormone Refractory Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Bone Metastasis-free Survival [ Time Frame: From the first dose of investigational product to the primary data cutoff date of 30 July 2010; median time on study was approximately 20 months. ] [ Designated as safety issue: No ]
    The time to the first occurrence of bone metastasis (either symptomatic or asymptomatic) or death from any cause. Participants who did not experience bone metastasis or on-study death were censored at the last on-study contact date or the primary analysis data cutoff date, whichever came first. Median bone metastasis-free survival time was estimated using the Kaplan-Meier method.


Secondary Outcome Measures:
  • Time to First Bone Metastasis [ Time Frame: From the first dose of investigational product to the primary data cutoff date of 30 July 2010; median time on study was approximately 20 months. ] [ Designated as safety issue: No ]
    Time from randomization to the date of first occurrence of bone metastasis (either symptomatic or asymptomatic), excluding death. Participants who did not develop bone metastasis were censored at their last on-study bone assessment date or the primary analysis data cut-off date, whichever was first. Median time to first bone metastasis was estimated using the Kaplan-Meier method.

  • Overall Survival [ Time Frame: From the first dose of investigational product to the primary data cutoff date of 30 July 2010; median time on study was approximately 20 months. ] [ Designated as safety issue: No ]
    Time from randomization to the date of death. Participants who were still alive or lost to follow-up by the primary analysis data cut-off date were censored at their last contact date (on-study or during survival follow-up) or the primary analysis data cut-off date, whichever was first.


Enrollment: 1435
Study Start Date: February 2006
Study Completion Date: April 2014
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Participants received placebo subcutaneous injections every 4 weeks during the double-blind treatment phase. Participants then received open-label denosumab 120 mg by subcutaneous injection every 4 weeks during the open-label extension phase.
Biological: Placebo
Same volume subcutaneous injection
Experimental: Denosumb
Participants received 120 mg denosumab administered by subcutaneous injection every 4 weeks during the double-blind treatment phase. Participants then received open-label denosumab 120 mg by subcutaneous injection every 4 weeks during the open-label extension phase.
Biological: Denosumab
Administered by subcutaneous injection
Other Name: XGEVA®

Detailed Description:

Participants were randomized to receive denosumab 120 mg or placebo every 4 weeks (Q4W) until approximately 660 participants developed bone metastasis or died and the primary efficacy and safety analyses were completed.

All participants undergoing scheduled assessments were offered open-label denosumab 120 mg subcutaneous (SC) until they either developed a bone metastasis, obtained access to commercially available product in this setting, or for up to 3 years, whichever came first. For participants who ended participation before the open-label extension (OLE) phase or withdrew from investigational product during the OLE phase, their survival data was to be collected every 6 months for up to 3 years after their last dose of investigational product.

Participants in the Czech Republic and United Kingdom were enrolled under a separate protocol for the OLE phase per Health Authority request, and are reported separately (Study 20080585; NCT01824342).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • men with histologically confirmed prostate cancer
  • bilateral orchiectomy at least 6 months before randomization or continuous androgen-deprivation therapy (ADT) with a gonadotropin releasing hormone (GnRH) agonist or antagonist for at least 6 months before randomization
  • total testosterone level less than 50 ng/dL,
  • hormone refractory (androgen independent) prostate cancer demonstrated during continuous ADT/post-orchiectomy defined as: 3 consecutive prostate-specific antigen (PSA) values with PSA1 < PSA2 < PSA3, each PSA value must be separated by at least 2 weeks, PSA2 and PSA3 greater than or equal to 1.0 ng/mL,
  • high risk for development of bone metastasis defined as PSA value greater than or equal to 8.0 ng/mL, obtained no more than 3 months before randomization OR PSA doubling time less than or equal to 10.0 months

Exclusion Criteria:

  • prior or current evidence of radiographically detectable bone metastasis
  • known prior or current evidence of any metastatic involvement of distant organs (lymph node metastases in any region is acceptable)
  • prior or current intravenous bisphosphonate administration
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00286091

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Publications:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00286091     History of Changes
Other Study ID Numbers: 20050147
Study First Received: February 2, 2006
Results First Received: March 25, 2015
Last Updated: May 20, 2015
Health Authority: Australia: Therapeutic Goods Administration
Canada: Health Canada
EU: EMEA
United States: Food and Drug Administration

Keywords provided by Amgen:
Hormone refractory prostate cancer
androgen independent
ADT
bone metastasis

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on September 03, 2015