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

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ClinicalTrials.gov Identifier: NCT00242567

Recruitment Status : Completed

First Posted : October 20, 2005

Results First Posted : March 6, 2013

Last Update Posted : May 7, 2014

Sponsor:

Information provided by (Responsible Party):

Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: Zoledronic Acid Drug: Androgen Deprivation Therapy (ADT)	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	522 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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.
Study Start Date :	December 2005
Actual Primary Completion Date :	January 2012
Actual Study Completion Date :	January 2012

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Prostate cancer

MedlinePlus related topics: Prostate Cancer

Drug Information available for: Zoledronic acid

U.S. FDA Resources

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures :

Skeletal-related Event-free Survival in Men With Bone Metastases From Prostate Cancer [ Time Frame: 18 months ]
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.

Secondary Outcome Measures :

Overall Survival at 18 Months and 3 Years [ Time Frame: month 18, year 3 ]
Overall survival (OS) time was measured from the start of study drug to the date of death due to any cause.
Time to Occurrence of Skeletal Related Event or Death [ Time Frame: 18 Months ]
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.
Skeletal-related Event(SRE)-Free Survival [ Time Frame: 36 months ]
Time from randomization until the first detected SRE. Patients who were still SRE-free at 3 years were censored.
Time to Occurrence of Skeletal Related Event or Death [ Time Frame: 36 Months ]
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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00242567

Locations

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

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

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Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals

More Information

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Responsible Party:	Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00242567
Other Study ID Numbers:	CZOL446E2432
First Posted:	October 20, 2005 Key Record Dates
Results First Posted:	March 6, 2013
Last Update Posted:	May 7, 2014
Last Verified:	April 2014

Keywords provided by Novartis ( Novartis Pharmaceuticals ):


zoledronic acid bone metastases prostate cancer hormone-sensitive

Additional relevant MeSH terms:

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Prostatic Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Neoplasms Prostatic Diseases	Zoledronic Acid Androgens Bone Density Conservation Agents Physiological Effects of Drugs Hormones Hormones, Hormone Substitutes, and Hormone Antagonists

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