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

Phase 3

Completed

• Conditions: Hormone Refractory Prostate Cancer
• Interventions: Biological: Denosumab; Biological: Placebo

• Registration Number: NCT00286091
• Lead Sponsor: Amgen

Brief Summary

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.

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).

Study Timeline

• Study Start: 2006-01-24
• Study First Submitted: 2006-02-02
• Study First Submitted QC: 2006-02-02
• Study First Posted: 2006-02-03
• Primary Completion: 2010-07-30
• Disposition First Submitted: 2011-05-26
• Disposition First Submitted QC: 2011-05-26
• Disposition First Posted: 2011-06-03
• Study Completion: 2014-04-09
• Results First Submitted: 2015-03-25
• Results First Submitted QC: 2015-03-25
• Results First Posted: 2015-04-06
• Status Verified: 2018-09
• Last Update Submitted: 2018-09-20
• Last Update Posted: 2018-10-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 1435

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Denosumb	Denosumab	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.
Placebo	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.

Primary Outcome Measures

Name	Time	Method
Bone Metastasis-free Survival	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.	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

Name	Time	Method
Overall Survival	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.	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.
Time to First Bone Metastasis	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.	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.