Study of Denosumab vs. Zoledronic Acid to Treat Bone Metastases in Men With Hormone-refractory Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if denosumab is non-inferior to zoledronic acid (Zometa®) in the treatment of bone metastases in men with hormone-refractory prostate cancer

Official Title
-----------------
A Randomized, Double-Blind, Multicenter Study of Denosumab Compared With Zoledronic Acid (Zometa®) in the Treatment of Bone Metastases in Men With Hormone-Refractory Prostate Cancer

Conditions
-----------------
Bone Metastases

Intervention / Treatment
-----------------
* Drug: zoledronic acid
* Biological: denosumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men >/= 18 years of age with histologically confirmed prostate cancer Radiographic evidence of at least one bone metastasis Failure of at least one hormonal therapy as evidenced by a rising PSA Serum testosterone level of <50 ng/dL ECOG PS 0, 1, or 2 Adequate organ function Exclusion Criteria: Current or prior IV bisphosphonate administration Current or prior oral bisphosphonates for bone mets Life expectancy of less than 6 months

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: zoledronic acid<br> | Drug: zoledronic acid<br>* Q4W 4 mg zoledronic acid IV over minimum 15 minutes and 120 mg denosumab placebo SC<br>* Other names: Zometa;|
| Experimental: denosumab<br> | Biological: denosumab<br>* Q4W 120 mg denosumab SC and 4 mg zoledronic acid placebo IV over a minimum of 15 minutes<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the First On-Study SRE (Non-inferiority) | Time to the first on-study skeletal-related event (SRE) analyzed for non-inferiority. Kaplan-Meier estimates of the median and its dispersion are reported. | Up to 40.5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the First On-Study SRE (Superiority) | Time to the first on-study skeletal-related event (SRE), analyzed for superiority of denosumab. Kaplan-Meier estimates of the median and its dispersion are reported. | Up to 40.5 months | 
| Time to the First-And-Subsequent On-Study SRE | Time to the first-and-subsequent on-study skeletal-related event (SRE), analyzed for superiority of denosumab using multiple event analysis, the event must occur at least 21 days after the previous SRE. This outcome measure utilizes multiple event times, was analyzed based on a proportional mean model, and is therefore more appropriately summarized by the cumulative mean number of events. | Up to 40.5 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bone metastases, Hormone-refractory prostate cancer, Skeletal, Fractures, Compressions, Bisphosphonates