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

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.

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

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Zoledronic Acid; Drug: Androgen Deprivation Therapy (ADT)

• Study Type: Interventional
• Enrollment (Actual): 522
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • Novartis Investigative Site
  • Brisbane, Australia
    • Novartis Investigative Site
  • Melbourne, Australia
    • Novartis Investigative Site
  • Port Macquarie, Australia
    • Novartis Investigative Site
  • Sydney, Australia
    • Novartis Investigative Site
• Brazil
  • Porto Alegre, Brazil
    • Novartis Investigative Site
  • Santo Andre, Brazil
    • Novartis Investigative Site
  • Sao Paulo, Brazil
    • Novartis Investigative Site
• China
  • Beijing, China
    • Novartis Investigative Site
  • Chongqing, China
    • Novartis Investigative Site
  • Shanghai, China
    • Novartis Investigative Site
• Korea, Republic of
  • Busan, Korea, Republic of
    • Novartis Investigative Site
  • Kyunggi-do, Korea, Republic of
    • Novartis Investigative Site
  • Seoul, Korea, Republic of
    • Novartis Investigative Site
• Kuwait
  • Kuwait, Kuwait
    • Novartis Investigative Site
• Lebanon
  • Beirut, Lebanon
    • Novartis Investigative Site
• New Zealand
  • Auckland, New Zealand
    • Novartis Investigative Site
  • Christchurch, New Zealand
    • Novartis Investigative Site
  • Hamilton, New Zealand
    • Novartis Investigative Site
  • Tauranga, New Zealand
    • Novartis Investigative Site
  • Wellington, New Zealand
    • Novartis Investigative Site
• Saudi Arabia
  • Riyadh, Saudi Arabia
    • Novartis Investigative Site
• Taiwan
  • Taichung, Taiwan
    • Novartis Investigative Site
  • Taipei, Taiwan
    • Novartis Investigative Site
  • Taoyuan, Taiwan
    • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand
    • Novartis Investigative Site
  • Songkhla, Thailand
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early Group; Zoledronic acid 4 mg i.v. infusion every 4 weeks, commencing at Baseline.	Drug: Zoledronic Acid; 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.
Experimental: Delayed group; 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); 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: October 19, 2005
• First Submitted That Met QC Criteria: October 19, 2005
• First Posted (Estimate): October 20, 2005

Study Record Updates

• Last Update Posted (Estimate): May 7, 2014
• Last Update Submitted That Met QC Criteria: April 14, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: prostate cancer; bone metastases; zoledronic acid; hormone-sensitive
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bone Density Conservation Agents; Zoledronic Acid; Androgens
• Other Study ID Numbers: CZOL446E2432