Study of Zoledronic Acid for Patients With Hormone-sensitive Bone Metastases From Prostate Cancer

Study Overview
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Brief Summary
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This study aims to determine whether early treatment with zoledronic acid, that is given during the early phase of advanced prostate cancer, will be more efficacious than delayed treatment

Official Title
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A Phase III, Parallel Group, Randomized, Open-label, Multi-centre Clinical Trial of Zoledronic Acid in Males Receiving Androgen Deprivation Therapy for Advanced Prostate Cancer.

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Zoledronic Acid
* Drug: Androgen Deprivation Therapy (ADT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: prostate cancer at least one bone metastasis receiving or about to receive androgen deprivation therapy (ADT) Exclusion Criteria: previous ADT failure previous or current treatment with another bone-protecting agent, chemotherapy or targeted therapy abnormal renal function Other protocol-defined inclusion/exclusion criteria may apply.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early Group<br>Zoledronic acid 4 mg i.v. infusion every 4 weeks, commencing at Baseline. | Drug: Zoledronic Acid<br>* Zoledronic acid was provided by Novartis in vials containing 4 mg/5 mL liquid concentrate. Prior to administration, the liquid concentrate from one vial was to be further diluted with 100 mL of calcium-free infusion solution (0.9 % weight by volume sodium chloride solution or 5 % weight by volume glucose solution). If refrigerated, the solution had to be allowed to reach room temperature before administration. After addition of the liquid concentrate to the infusion media, the infusion solution was to be used as soon as practicable to reduce the risk of microbiological hazard. If storage of the solution was necessary, it had to be refrigerated at temperatures between 2-8 degrees C and was to be used within 24 hours. The infusion solution containing 4 mg zoledronic acid was to be administered every 4 weeks as an i.v. infusion over no less than 15 minutes.<br>|
| Experimental: Delayed group<br>Zoledronic acid 4 mg i.v. infusion every 4 weeks, commencing no sooner than 12 months after their baseline visit, and not until they have had three rises in PSA level from Baseline, one of which must be a least 10 ng/mL greater than the baseline Serum Prostate-specific Antigen (PSA) level. | Drug: Androgen Deprivation Therapy (ADT)<br>* Androgen deprivation therapy (ADT) was to be administered according to institutional protocols, in accordance with relevant prescribing information. The type and duration of androgen deprivation was at the discretion of the treating specialist, and could include orchiectomy where this would normally have been performed. Androgen deprivation therapy was provided by the investigational center, or obtained by the patient from usual sources. Anti-androgen monotherapy and intermittent ADT were excluded in the first 12 months of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skeletal-related Event-free Survival in Men With Bone Metastases From Prostate Cancer | Skeletal-related event free survival is the time from randomization until the first detected Skeletal Related Event (SRE). Patients who were still SRE-free at 18 months were censored. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival at 18 Months and 3 Years | Overall survival (OS) time was measured from the start of study drug to the date of death due to any cause. | month 18, year 3 | 
| Time to Occurrence of Skeletal Related Event or Death | Time from randomization to the first detected skeletal related event or death. This endpoint is the same as the primary endpoint with the modification that deaths are considered events. | 18 Months | 
| Skeletal-related Event(SRE)-Free Survival | Time from randomization until the first detected SRE. Patients who were still SRE-free at 3 years were censored. | 36 months | 
| Time to Occurrence of Skeletal Related Event or Death | Time from randomization to the first detected skeletal related event or death. This endpoint is the same as the primary endpoint with the modification that deaths are considered events. | 36 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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zoledronic acid, bone metastases, prostate cancer, hormone-sensitive