Study of Denosumab vs. Zoledronic Acid to Treat Bone Metastases in Subjects With Advanced Cancer or Multiple Myeloma.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00330759
First received: May 25, 2006
Last updated: July 14, 2014
Last verified: July 2014
Results First Received: December 9, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Supportive Care
Condition: Bone Metastases
Interventions: Biological: Denosumab
Drug: Zoledronic Acid

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were enrolled from 21 June 2006 through 16 May 2008

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 1779 participants were enrolled in the study. Three participants from one site were excluded from all analyses because Institutional Review Board (IRB) review activities and oversight were not ensured.

Reporting Groups
  Description
Zoledronic Acid Zoledronic acid 4 mg by intravenous injection with a subcutaneous denosumab placebo once every 4 weeks
Denosumab Denosumab 120 mg by subcutaneous injection with an intravenous zoledronic acid placebo once every 4 weeks

Participant Flow:   Overall Study
    Zoledronic Acid     Denosumab  
STARTED     890     886  
Received Investigational Product     878     878  
COMPLETED     178     180  
NOT COMPLETED     712     706  
Death                 316                 310  
Disease progression                 104                 126  
Withdrawal by Subject                 143                 124  
Adverse Event                 48                 36  
Participant request                 31                 22  
Lost to Follow-up                 16                 22  
Noncompliance                 15                 17  
Physician Decision                 1                 2  
Protocol deviation                 0                 2  
Ineligibility determined                 2                 1  
Other                 36                 44  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Zoledronic Acid Zoledronic acid 4 mg by intravenous injection with a subcutaneous denosumab placebo once every 4 weeks
Denosumab Denosumab 120 mg by subcutaneous injection with an intravenous zoledronic acid placebo once every 4 weeks
Total Total of all reporting groups

Baseline Measures
    Zoledronic Acid     Denosumab     Total  
Number of Participants  
[units: participants]
  890     886     1776  
Age  
[units: Years]
Mean ± Standard Deviation
  60.6  ± 10.7     59.3  ± 11.4     59.9  ± 11.1  
Gender  
[units: Participants]
     
Female     338     298     636  
Male     552     588     1140  
Race/Ethnicity, Customized  
[units: Participants]
     
White or Caucasian     770     770     1540  
Black or African American     29     20     49  
Hispanic or Latino     36     49     85  
Asian     44     36     80  
Japanese     1     3     4  
American Indian or Alaska Native     2     0     2  
Other     8     8     16  
Tumor Type Stratification Factor  
[units: Participants]
     
Multiple myeloma     93     86     179  
Other     452     457     909  
Non-small cell lung cancer     345     343     688  
Previous Skeletal-Related Event Stratification Factor  
[units: Participants]
     
Yes     446     440     886  
No     444     446     890  
Systematic Anti-Cancer Therapy Stratification Factor  
[units: Participants]
     
Yes     747     746     1493  
No     143     140     283  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Time to the First On-Study Skeletal-Related Event (Non-Inferiority)   [ Time Frame: up to 33 months ]

2.  Secondary:   Time to First On-Study Skeletal-Related Event (Superiority)   [ Time Frame: up to 33 months ]

3.  Secondary:   Time to the First-and-Subsequent On-Study Skeletal-Related Event   [ Time Frame: up to 33 months ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Amgen Inc.
phone: 866-572-6436


Publications:
Henry D, Costa L, Goldwasser F, Hirsh V, Hungria V, Prausova J, Scagliotti GV, Sleeboom H, Spencer A, Vadhan-Raj S, von Moos R, Willenbacher W, Woll PJ, Wang J, Jiang Q, Jun S, Dansey R, Yeh H. Randomized, Double-Blind Study of Denosumab Versus Zoledronic Acid in the Treatment of Bone Metastases in Patients With Advanced Cancer (Excluding Breast and Prostate Cancer) or Multiple Myeloma. Journal of Clinical Oncology;2011;29(9);1125-1132

Publications automatically indexed to this study:

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00330759     History of Changes
Other Study ID Numbers: 20050244
Study First Received: May 25, 2006
Results First Received: December 9, 2010
Last Updated: July 14, 2014
Health Authority: Russia: Ministry of Health
Russia: Ministry of Health,
Slovakia: 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
Canada: Health Products and Food Branch
Canada: Health Products and Food Branch,
Canada: Institutional Review Board
Chile: Health Ministry
Chile: Health Ministry,
Czech Republic: State Institute for Drug Control
Czech Republic: Statni ustav pro kontrolu leciv
European Union: European Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
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
Greece: National Organization for Medicines
Greece: National Organization for Medicines,
Hungary: Ministry of Health, Social and Family Affairs
Hungary: National Institute of Pharmacy
India: Central Drugs Standard Control Organization
Israel: Ministry of Health
Italy: Local Ethics Committees
Italy: Ministry of Health
Latvia: State Agency of Medicines
Latvia: State Agency of Medicines, Lithuania: Ministry of Health,
Lithuania: Ministry of Health
Lithuania: State Medicines Control Agency of Lithuania
Mexico: COFEPRIS
Mexico: Ministry of Health
Mexico: Ministry of Health, Netherlands: Medicines Evaluation Board,
Mexico: SSA (Secretaria de Salud Publica)
Slovakia: Ministry of Health,
Slovakia: State Institiute for Drug Control
Slovakia: Štátny ústav pre kontrolu lieciv
South Africa: Department of Health
South Africa: Department of Health, Spain: Spanish Drug Agency,
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Spanish Agency of Medicines
Spain: Spanish Drug Agency
Sweden: Central Ethics Committee
Sweden: Lakemedelsverket
Sweden: Medical Products Agency
Switzerland: Agency for Therapeutic Products
Switzerland: Local Ethics Committee
Switzerland: Swissmedic (Swiss Agency for Therapeutic Products)
Turkey: Ministry of Health, United Kingdom: Medicines and Healthcare Products Regulatory Agency,
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
United States: Institutional Review Board
United States: IntegReview Ethical Review Board
United States: Quorom Institutional Review Board
United States: Western Institutional Review Board
Russia: Federal Service for Surveillance in the field of Healthcare and Social Development (a body of the Ministry of Health)
Argentina: ANMAT (Administracion Nacional de Medicamentos Alimentos y Tecnologia Medica)
Argentina: Ministry of Health
Argentina: Ministry of Health, Australia: Therapeutic Goods Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: Human Research Ethics Committee
Australia: Therapeutic Goods Administration
Austria: AGES - PharmaMed Austria Institut Wissenschaft & Information
Austria: Bundesamt fur Sicherheit im Gesundheitswesen
Austria: Bundesamt für Sicherheit im Gesundheitswesen
Austria: Central Ethics Committee
Austria: Competant Authority
Austria: Federal Ministry for Health and Women
Austria: Secretariat of Health
Austria: Secretariat of Health, Belgium: Pharmaceutical Inspectorate,
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
Netherlands: CCMO (Centrale Commissie Mensgebonden Onderzoek): Central Committee Human Bound Research
Netherlands: Medicines Evaluation Board
Netherlands: Medisch Centrum Rijnmond_Zuid, lcatie Zuider
Panama: Ministry of Health
Peru: INS (Instituto Nacional de Salud)
Peru: Ministry of Health
Poland: Drug Institut
Poland: Drug Institut,
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: Instituto Nacional da Farmácia e do Medicamento (INFARMED)
Portugal: National Institute of Pharmacy and Medicines
Portugal: National Institute of Pharmacy and Medicines,
Romaina: National Medicines Agency
Romania: Ministry of Health and the Family
Romania: Ministry of Health and the Family,
Romania: Romanian National Drug Agency