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

This study has been completed.
Information provided by (Responsible Party):
Amgen Identifier:
First received: May 25, 2006
Last updated: July 14, 2014
Last verified: July 2014
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


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

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 identifier: NCT00330759

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

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasm Metastasis
Neoplasms, Second Primary
Bone Neoplasms
Bone Marrow Diseases
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
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
Bone Density Conservation Agents
Physiological Effects of Drugs processed this record on December 09, 2016