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
  Purpose

The purpose of this study is to determine if denosumab is non-inferior to zoledronic acid (Zometa®) in the treatment of bone metastases (lytic bone lesions from multiple myeloma) in subjects with advanced cancer and multiple myeloma (excluding breast and prostate 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, 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 Cancer (Excluding Breast and Prostate Cancer) or Multiple Myeloma.

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Time to the First On-Study Skeletal-Related Event (Non-Inferiority) [ Time Frame: up to 33 months ] [ Designated as safety issue: No ]
    Time to the first on-study skeletal-related event (SRE) using a non-inferiority analysis. Median was estimated using the Kaplan-Meier method.


Secondary Outcome Measures:
  • Time to First On-Study Skeletal-Related Event (Superiority) [ Time Frame: up to 33 months ] [ Designated as safety issue: No ]
    Time to first on-study skeletal-related event (SRE) using a test for superiority. Median was estimated using the Kaplan-Meier method.

  • Time to the First-and-Subsequent On-Study Skeletal-Related Event [ Time Frame: up to 33 months ] [ Designated as safety issue: No ]

    Time to the first-and-subsequent on-study skeletal-related event (SRE) using 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 mean number of events.



Enrollment: 1779
Study Start Date: June 2006
Study Completion Date: October 2011
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: zoledronic acid
denosumab placebo with active zoledronic acid
Drug: Zoledronic Acid
4 milligrams intravenous Zoledronic Acid over minimum 15 minutes every 4 weeks
Other Name: Zometa
Experimental: denosumab
active denosumab with zoledronic acid placebo
Biological: Denosumab
120 milligrams by subcutaneous injection every 4 weeks

  Eligibility

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

Inclusion Criteria:

  • Adults with histologically/cystologically confirmed advanced cancers including solid tumors, multiple myeloma, and lymphoma
  • Radiographic evidence of at least one bone metastasis (or lytic bone lesion from multiple myeloma); ECOG performance status 0, 1, or 2
  • Adequate organ function

Exclusion Criteria:

  • Diagnosis of breast or prostate cancer
  • Current or prior intravenous bisphosphonate administration
  • Current or prior oral bisphosphonates for bone metastases, life expectancy of less than 6 months
  • Prior history or current evidence of osteonecrosis/osteomyelitis of the jaw
  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 ClinicalTrials.gov identifier: NCT00330759

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
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

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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
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European Union: European Medicines Agency
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France: CCPPRB Central Ethics Committee
France: Ministry of Health
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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
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Mexico: COFEPRIS
Mexico: Ministry of Health
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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
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Austria: AGES - PharmaMed Austria Institut Wissenschaft & Information
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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

Keywords provided by Amgen:
Bone metastases
lytic bone lesions
advanced cancer
multiple myeloma
lymphoma
solid tumors
skeletal related events
skeletal fractures
spinal cord compressions, radiation to bone
surgery to bone, bisphosphonates
denosumab

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasm Metastasis
Neoplasms, Second Primary
Bone Neoplasms
Bone Marrow Diseases
Neoplasms
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Neoplastic Processes
Pathologic Processes
Neoplasms by Site
Bone Diseases
Musculoskeletal Diseases
Zoledronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014