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

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

Conditions
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Hormone Refractory Prostate Cancer

Intervention / Treatment
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* Biological: Denosumab
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>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<br>* Same volume subcutaneous injection<br>|
| Experimental: Denosumb<br>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<br>* Administered by subcutaneous injection<br>* Other names: XGEVA®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Metastasis-free Survival | 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. | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Bone Metastasis | 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. | 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. | 
| Overall Survival | 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. | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hormone refractory prostate cancer, androgen independent, ADT, bone metastasis