NCT00321620

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 in men with hormone-refractory prostate cancer

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,904

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Apr 2006

Longer than P75 for phase_3

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2006

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

May 2, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 4, 2006

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2009

Completed
2.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 24, 2012

Completed
2.1 years until next milestone

Results Posted

Study results publicly available

March 21, 2014

Completed
Last Updated

August 29, 2018

Status Verified

August 1, 2018

Enrollment Period

3.5 years

First QC Date

May 2, 2006

Results QC Date

December 10, 2010

Last Update Submit

August 1, 2018

Conditions

Bone Metastases

Keywords

Bone metastasesHormone-refractory prostate cancerSkeletalFracturesCompressionsBisphosphonates

Outcome Measures

Primary Outcomes (1)

  • Time to the First On-Study SRE (Non-inferiority)

    Time to the first on-study skeletal-related event (SRE) analyzed for non-inferiority. Kaplan-Meier estimates of the median and its dispersion are reported.

    Up to 40.5 months

Secondary Outcomes (2)

  • Time to the First On-Study SRE (Superiority)

    Up to 40.5 months

  • Time to the First-And-Subsequent On-Study SRE

    Up to 40.5 months

Study Arms (2)

zoledronic acid

ACTIVE COMPARATOR
Drug: zoledronic acid

denosumab

EXPERIMENTAL
Biological: denosumab

Interventions

zoledronic acidDRUG

Q4W 4 mg zoledronic acid IV over minimum 15 minutes and 120 mg denosumab placebo SC

Also known as: Zometa
zoledronic acid
denosumabBIOLOGICAL

Q4W 120 mg denosumab SC and 4 mg zoledronic acid placebo IV over a minimum of 15 minutes

denosumab

Eligibility Criteria

Age18 Years+
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Men \>/= 18 years of age with histologically confirmed prostate cancer
  • Radiographic evidence of at least one bone metastasis
  • Failure of at least one hormonal therapy as evidenced by a rising PSA
  • Serum testosterone level of \<50 ng/dL
  • ECOG PS 0, 1, or 2
  • Adequate organ function

You may not qualify if:

  • Current or prior IV bisphosphonate administration
  • Current or prior oral bisphosphonates for bone mets
  • Life expectancy of less than 6 months

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (9)

  • Fizazi K, Carducci M, Smith M, Damiao R, Brown J, Karsh L, Milecki P, Shore N, Rader M, Wang H, Jiang Q, Tadros S, Dansey R, Goessl C. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet. 2011 Mar 5;377(9768):813-22. doi: 10.1016/S0140-6736(10)62344-6. Epub 2011 Feb 25.

    PMID: 21353695BACKGROUND

  • Smith MR, Coleman RE, Klotz L, Pittman K, Milecki P, Ng S, Chi KN, Balakumaran A, Wei R, Wang H, Braun A, Fizazi K. Denosumab for the prevention of skeletal complications in metastatic castration-resistant prostate cancer: comparison of skeletal-related events and symptomatic skeletal events. Ann Oncol. 2015 Feb;26(2):368-74. doi: 10.1093/annonc/mdu519. Epub 2014 Nov 25.

    PMID: 25425475BACKGROUND

  • Fizazi K, Massard C, Smith M, Rader M, Brown J, Milecki P, Shore N, Oudard S, Karsh L, Carducci M, Damiao R, Wang H, Ying W, Goessl C. Bone-related Parameters are the Main Prognostic Factors for Overall Survival in Men with Bone Metastases from Castration-resistant Prostate Cancer. Eur Urol. 2015 Jul;68(1):42-50. doi: 10.1016/j.eururo.2014.10.001. Epub 2014 Oct 29.

    PMID: 25449207BACKGROUND

  • Jakob T, Tesfamariam YM, Macherey S, Kuhr K, Adams A, Monsef I, Heidenreich A, Skoetz N. Bisphosphonates or RANK-ligand-inhibitors for men with prostate cancer and bone metastases: a network meta-analysis. Cochrane Database Syst Rev. 2020 Dec 3;12(12):CD013020. doi: 10.1002/14651858.CD013020.pub2.

    PMID: 33270906DERIVED

  • Stopeck AT, Fizazi K, Body JJ, Brown JE, Carducci M, Diel I, Fujiwara Y, Martin M, Paterson A, Tonkin K, Shore N, Sieber P, Kueppers F, Karsh L, Yardley D, Wang H, Maniar T, Arellano J, Braun A. Safety of long-term denosumab therapy: results from the open label extension phase of two phase 3 studies in patients with metastatic breast and prostate cancer. Support Care Cancer. 2016 Jan;24(1):447-455. doi: 10.1007/s00520-015-2904-5. Epub 2015 Sep 3.

    PMID: 26335402DERIVED

  • 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.

    PMID: 26093811DERIVED

  • de Liano AG, Reig O, Mellado B, Martin C, Rull EU, Maroto JP. Prognostic and predictive value of plasma testosterone levels in patients receiving first-line chemotherapy for metastatic castrate-resistant prostate cancer. Br J Cancer. 2014 Apr 29;110(9):2201-8. doi: 10.1038/bjc.2014.189. Epub 2014 Apr 10.

    PMID: 24722180DERIVED

  • 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.

    PMID: 23975226DERIVED

  • 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.

    PMID: 22975218DERIVED

Related Links

MeSH Terms

Conditions

Fractures, Bone

Interventions

Zoledronic AcidDenosumab

Condition Hierarchy (Ancestors)

Wounds and Injuries

Intervention Hierarchy (Ancestors)

DiphosphonatesOrganophosphonatesOrganophosphorus CompoundsOrganic ChemicalsImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Results Point of Contact

Title
Study Director
Organization
Amgen Inc.
866-572-6436

Study Officials

  • MD

    Amgen

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
SUPPORTIVE CARE
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 2, 2006

First Posted

May 4, 2006

Study Start

April 1, 2006

Primary Completion

October 1, 2009

Study Completion

February 24, 2012

Last Updated

August 29, 2018

Results First Posted

March 21, 2014

Record last verified: 2018-08