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A Study Comparing Denosumab vs. Zoledronic Acid for the Treatment of Bone Metastases in Breast Cancer Subjects.

This study has been completed.
Daiichi Sankyo Inc.
Information provided by (Responsible Party):
Amgen Identifier:
First received: May 2, 2006
Last updated: July 11, 2014
Last verified: July 2014
The purpose of this study is to determine if denosumab is non-inferior to zoledronic acid in the treatment of bone metastases in subjects with advanced breast cancer.

Condition Intervention Phase
Bone Metastases
Biological: Denosumab
Drug: Zoledronic Acid
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
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 Subjects With Advanced Breast Cancer

Resource links provided by NLM:

Further study details as provided by Amgen:

Primary Outcome Measures:
  • Time to First On-Study Skeletal Related Event (SRE) (Non-inferiority) [ Time Frame: Up to 34 months ] [ Designated as safety issue: No ]
    Time to first on-study skeletal-related event (SRE) using a non-inferiority analysis. The median time to first skeletal-related event could not be estimated in one treatment arm, so the subject incidence is presented.

Secondary Outcome Measures:
  • Time to First On-Study Skeletal-Related Event (Superiority) [ Time Frame: Up to 34 months ] [ Designated as safety issue: No ]
    Time to first on-study skeletal-related event (SRE) using a superiority analysis. The median time to first skeletal-related event could not be estimated in one treatment arm, so the subject incidence is presented.

  • Time to First and Subsequent On-Study Skeletal-Related Event [ Time Frame: Up to 34 months ] [ Designated as safety issue: No ]
    Time to first and subsequent on-study skeletal-related event (SRE) using a multiple event analysis. To be considered a subsequent SRE, 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 number of events.

Enrollment: 2049
Study Start Date: April 2006
Study Completion Date: April 2012
Primary Completion Date: March 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 injection and 4 mg zoledronic acid (Zometa) placebo IV over a minimum of 15 minutes


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Adults with histologically or cytologically confirmed breast adenocarcinoma
  • radiographic evidence of at least one bone mets
  • Easter Cooperative Oncology Group status of 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: NCT00321464

Sponsors and Collaborators
Daiichi Sankyo Inc.
Study Director: MD Amgen
  More Information

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

Responsible Party: Amgen Identifier: NCT00321464     History of Changes
Other Study ID Numbers: 20050136 
Study First Received: May 2, 2006
Results First Received: December 10, 2010
Last Updated: July 11, 2014
Health Authority: South Africa: Department of Health, Spain: Spanish Drug Agency, Sweden: Medical Products Agency, Switzerland: Agency for Therapeutic Products
Spain: Spanish Agency of Medicines
Spain: Spanish Drug Agency
Sweden: Central Ethics Committee
Sweden: Medical Products Agency
Switzerland: Agency for Therapeutic Products
Switzerland: Local Ethics Committee
Switzerland: Swissmedic (Swiss Agency for Therapeutic Products)
Turkey: Ministry of Health
Ukraine: Ministry of Health
Ukraine: Pharmacological Centre at the Ministry of Health of the Ukraine (Pharma Centre)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Argentina: Ministry of Health, Australia: Therapeutic Goods Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: Therapeutic Goods Administration
Austria: Secretariat of Health, Belgium: Pharmaceutical Inspectorate Brazil: Ministry of Health
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Belgium: Directorate-General for Medicinal Products
Belgium: Federal Public Service (FPS) Health, Food Chain Safety and Environment
Czech Republic: State Institute for Drug Control
Denmark: Ministry of Health
Belgium: FPS of Public Health, Food Chain Security and Environment
Belgium: Pharmaceutical Inspectorate
Belgium: Service Public Federal Sante Publiquest, Securite de la Chaine alimentaire et Environnement
Belgium: Service Public Fédéral Santé Publique, Sécurité de la Chaîne alimentaire et Environnement
Brazil: ANVISA (Agência Nacional de Vigilância Sanitária)
Brazil: Ministry of Health
Bulgaria: Bulgarian Drug Agency
Bulgaria: Ministry of Health
Canada: Health Canada
Finland: Lääkelaitos
France and Sweden: European Medicines Agency
France: CCPPRB Central Ethics Committee
France: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Germany: Paul_Ehrlich-Institut Bundesamt fur Sera und Impfstoffe
Hungary: National Institute of Pharmacy
India: Central Drugs Standard Control Organization
Israel: Ministry of Health
Italy: Ministry of Health
Japan: Ministry of Health, Labor and Welfare
Japan: Pharmaceuticals and Medical Devices Evaluation Center
Latvia: State Agency of Medicines, Mexico: Ministry of Health
Lithuania: Ministry of Health
Mexico: SSA (Secretaria de Salud Publica)
Netherlands: CCMO (Centrale Commissie Mensgebonden Onderzoek): Central Committee Human Bound Research
Netherlands: Medicines Evaluation Board
Panama: Ministry of Health
Peru: Ministry of Health
Poland: Drug Institut
Romaina: National Medicines Agency
Romania: Ministry of Health and the Family
Romania: Romanian National Drug Agency
Russia: Federal Service for Surveillance in the field of Healthcare and Social Development (a body of the Ministry of Health)
Russia: Ministry of Health
Slovakia: Ministry of Health
Slovakia: State Institiute for Drug Control
South Africa: Department of Health
Canada: Health Products and Food Branch
Canada: Institutional Review Board
Chile: Health Ministry
Estonia: State Agency of Medicines, France: Ministry of Health
European Union: European Medicines Agency

Keywords provided by Amgen:
Bone metastases
Breast cancer
Surgery to Bone

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Bone Neoplasms
Neoplasms by Site
Breast Diseases
Bone Marrow Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Bone Diseases
Musculoskeletal Diseases
Hematologic Diseases
Zoledronic acid
Bone Density Conservation Agents
Physiological Effects of Drugs processed this record on January 18, 2017