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

Primary Purpose

Bone Metastases

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Denosumab
Zoledronic Acid
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Bone Metastases focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Experimental

    Arm Label

    zoledronic acid

    denosumab

    Arm Description

    denosumab placebo with active zoledronic acid

    active denosumab with zoledronic acid placebo

    Outcomes

    Primary Outcome Measures

    Time to the First On-Study Skeletal-Related Event (Non-Inferiority)
    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 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 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.

    Full Information

    First Posted
    May 25, 2006
    Last Updated
    November 4, 2022
    Sponsor
    Amgen
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00330759
    Brief Title
    Study of Denosumab vs. Zoledronic Acid to Treat Bone Metastases in Subjects With Advanced Cancer or Multiple Myeloma.
    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.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2022
    Overall Recruitment Status
    Completed
    Study Start Date
    June 1, 2006 (Actual)
    Primary Completion Date
    April 1, 2009 (Actual)
    Study Completion Date
    October 1, 2011 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Amgen

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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)

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Bone Metastases
    Keywords
    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

    7. Study Design

    Primary Purpose
    Supportive Care
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    1779 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    zoledronic acid
    Arm Type
    Active Comparator
    Arm Description
    denosumab placebo with active zoledronic acid
    Arm Title
    denosumab
    Arm Type
    Experimental
    Arm Description
    active denosumab with zoledronic acid placebo
    Intervention Type
    Biological
    Intervention Name(s)
    Denosumab
    Intervention Description
    120 milligrams by subcutaneous injection every 4 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Zoledronic Acid
    Other Intervention Name(s)
    Zometa
    Intervention Description
    4 milligrams intravenous Zoledronic Acid over minimum 15 minutes every 4 weeks
    Primary Outcome Measure Information:
    Title
    Time to the First On-Study Skeletal-Related Event (Non-Inferiority)
    Description
    Time to the first on-study skeletal-related event (SRE) using a non-inferiority analysis. Median was estimated using the Kaplan-Meier method.
    Time Frame
    up to 33 months
    Secondary Outcome Measure Information:
    Title
    Time to First On-Study Skeletal-Related Event (Superiority)
    Description
    Time to first on-study skeletal-related event (SRE) using a test for superiority. Median was estimated using the Kaplan-Meier method.
    Time Frame
    up to 33 months
    Title
    Time to the First-and-Subsequent On-Study Skeletal-Related Event
    Description
    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.
    Time Frame
    up to 33 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility 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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    MD
    Organizational Affiliation
    Amgen
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    24162260
    Citation
    Henry D, Vadhan-Raj S, Hirsh V, von Moos R, Hungria V, Costa L, Woll PJ, Scagliotti G, Smith G, Feng A, Jun S, Dansey R, Yeh H. Delaying skeletal-related events in a randomized phase 3 study of denosumab versus zoledronic acid in patients with advanced cancer: an analysis of data from patients with solid tumors. Support Care Cancer. 2014 Mar;22(3):679-87. doi: 10.1007/s00520-013-2022-1. Epub 2013 Oct 26.
    Results Reference
    background
    PubMed Identifier
    21343556
    Citation
    Henry DH, 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. J Clin Oncol. 2011 Mar 20;29(9):1125-32. doi: 10.1200/JCO.2010.31.3304. Epub 2011 Feb 22.
    Results Reference
    background
    PubMed Identifier
    23154554
    Citation
    Scagliotti GV, Hirsh V, Siena S, Henry DH, Woll PJ, Manegold C, Solal-Celigny P, Rodriguez G, Krzakowski M, Mehta ND, Lipton L, Garcia-Saenz JA, Pereira JR, Prabhash K, Ciuleanu TE, Kanarev V, Wang H, Balakumaran A, Jacobs I. Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study. J Thorac Oncol. 2012 Dec;7(12):1823-1829. doi: 10.1097/JTO.0b013e31826aec2b.
    Results Reference
    background
    PubMed Identifier
    22851406
    Citation
    Vadhan-Raj S, von Moos R, Fallowfield LJ, Patrick DL, Goldwasser F, Cleeland CS, Henry DH, Novello S, Hungria V, Qian Y, Feng A, Yeh H, Chung K. Clinical benefit in patients with metastatic bone disease: results of a phase 3 study of denosumab versus zoledronic acid. Ann Oncol. 2012 Dec;23(12):3045-3051. doi: 10.1093/annonc/mds175. Epub 2012 Jul 31.
    Results Reference
    background
    PubMed Identifier
    29972647
    Citation
    Abdel-Rahman O. Predictors of skeletal-related events among cancer patients with bone metastases treated with zoledronic acid: a secondary analysis of a randomized study. Expert Opin Drug Saf. 2018 Aug;17(8):757-761. doi: 10.1080/14740338.2018.1497157. Epub 2018 Jul 11.
    Results Reference
    derived
    PubMed Identifier
    26093811
    Citation
    Body JJ, Bone HG, de Boer RH, Stopeck A, Van Poznak C, Damiao R, Fizazi K, Henry DH, Ibrahim T, Lipton A, Saad F, Shore N, Takano T, Shaywitz AJ, Wang H, Bracco OL, Braun A, Kostenuik PJ. Hypocalcaemia in patients with metastatic bone disease treated with denosumab. Eur J Cancer. 2015 Sep;51(13):1812-21. doi: 10.1016/j.ejca.2015.05.016. Epub 2015 Jun 17.
    Results Reference
    derived
    PubMed Identifier
    25976743
    Citation
    Diel IJ, Body JJ, Stopeck AT, Vadhan-Raj S, Spencer A, Steger G, von Moos R, Goldwasser F, Feng A, Braun A. The role of denosumab in the prevention of hypercalcaemia of malignancy in cancer patients with metastatic bone disease. Eur J Cancer. 2015 Jul;51(11):1467-75. doi: 10.1016/j.ejca.2015.04.017. Epub 2015 May 11.
    Results Reference
    derived
    PubMed Identifier
    23975226
    Citation
    von Moos R, Body JJ, Egerdie B, Stopeck A, Brown JE, Damyanov D, Fallowfield LJ, Marx G, Cleeland CS, Patrick DL, Palazzo FG, Qian Y, Braun A, Chung K. Pain and health-related quality of life in patients with advanced solid tumours and bone metastases: integrated results from three randomized, double-blind studies of denosumab and zoledronic acid. Support Care Cancer. 2013 Dec;21(12):3497-507. doi: 10.1007/s00520-013-1932-2. Epub 2013 Aug 22.
    Results Reference
    derived
    PubMed Identifier
    22975218
    Citation
    Lipton A, Fizazi K, Stopeck AT, Henry DH, Brown JE, Yardley DA, Richardson GE, Siena S, Maroto P, Clemens M, Bilynskyy B, Charu V, Beuzeboc P, Rader M, Viniegra M, Saad F, Ke C, Braun A, Jun S. Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer. 2012 Nov;48(16):3082-92. doi: 10.1016/j.ejca.2012.08.002. Epub 2012 Sep 10.
    Results Reference
    derived
    Links:
    URL
    http://www.amgentrials.com
    Description
    AmgenTrials clinical trials website
    URL
    http://download.veritasmedicine.com/REGFILES/amgen/Amgen_results_disclaimer.pdf
    Description
    Notice regarding posted summaries of trial results

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

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