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

This study has been completed.
Information provided by (Responsible Party):
Amgen Identifier:
First received: May 2, 2006
Last updated: February 19, 2016
Last verified: February 2016
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

Condition Intervention Phase
Bone Metastases
Drug: zoledronic acid
Biological: denosumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
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

Resource links provided by NLM:

Further study details as provided by Amgen:

Primary Outcome Measures:
  • Time to the First On-Study SRE (Non-inferiority) [ Time Frame: Up to 40.5 months ] [ Designated as safety issue: No ]
    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.

Secondary Outcome Measures:
  • Time to the First On-Study SRE (Superiority) [ Time Frame: Up to 40.5 months ] [ Designated as safety issue: No ]
    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.

  • Time to the First-And-Subsequent On-Study SRE [ Time Frame: Up to 40.5 months ] [ Designated as safety issue: No ]

    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.

Enrollment: 1904
Study Start Date: April 2006
Study Completion Date: February 2012
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: zoledronic acid Drug: zoledronic acid
Q4W 4 mg zoledronic acid IV over minimum 15 minutes and 120 mg denosumab placebo SC
Other Name: Zometa
Experimental: denosumab Biological: denosumab
Q4W 120 mg denosumab SC and 4 mg zoledronic acid placebo IV over a minimum of 15 minutes


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00321620

Sponsors and Collaborators
Study Director: MD Amgen
  More Information

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):

Responsible Party: Amgen Identifier: NCT00321620     History of Changes
Other Study ID Numbers: 20050103 
Study First Received: May 2, 2006
Results First Received: December 10, 2010
Last Updated: February 19, 2016
Health Authority: Argentina: Ministry of Health
Australia: Therapeutic Goods Administration
Austria: Secretariat of Health
Belgium: Pharmaceutical Inspectorate
Brazil: Ministry of Health
Bulgaria: Ministry of Health
Canada: Health Products and Food Branch
Chile: Health Ministry
Czech Republic: State Institute for Drug Control
Denmark: Ministry of Health
Estonia: State Agency of Medicines
France: Ministry of Health
Germancy: Federal Institute for Drugs and Medical Devices
Greece: National Organization for Medicines
Guatemala: Ministry of Health
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Latvia: State Agency of Medicines
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Mexico: Ministry of Health
Netherlands: Medicines Evaluation Board
Norway: Norwegian Medicines Agency
Panama: Ministry of Health, Peru: Ministry of Health
Poland: Drug Institut
Portugal: National Institute of Pharmacy and Medicines
Russia: Ministry of Health
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South Africa: Department of Health
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Sweden: Medical Products Agency
Switzerland: Agency for Therapeutic Products
Turkey: Ministry of Health
Ukraine: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Romania: Ministry of Health and the Family

Keywords provided by Amgen:
Bone metastases
Hormone-refractory prostate cancer

Additional relevant MeSH terms:
Bone Marrow Diseases
Bone Neoplasms
Neoplasm Metastasis
Prostatic Neoplasms
Bone Diseases
Genital Diseases, Male
Genital Neoplasms, Male
Hematologic Diseases
Musculoskeletal Diseases
Neoplasms by Site
Neoplastic Processes
Pathologic Processes
Prostatic Diseases
Urogenital Neoplasms
Zoledronic acid
Bone Density Conservation Agents
Physiological Effects of Drugs processed this record on May 23, 2016