AzTrials
AzTrials

Bone MetastasesPhase 3NCT00321620

Study of Denosumab vs. Zoledronic Acid to Treat Bone Metastases in Men With Hormone-refractory Prostate Cancer

A Phase 3 study testing zoledronic acid and denosumab in people with Bone Metastases, run by Amgen.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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 Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Bone Metastases
What is being tested?
zoledronic acid and denosumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,904 participants
Where
No sites listed yet
Study dates
1 Apr 2006to 24 Feb 2012
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

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

About this study

Official title: A Randomized, Double-Blind, Multicenter Study of Denosumab Compared With Zoledronic Acid (Zometa®) in the Treatment of Bone Metastases in Men With Hormone-Refractory Prostate Cancer

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

Conditions
Bone Metastases
Being tested
zoledronic acid, denosumab
Keywords
Bone metastases, Hormone-refractory prostate cancer, Skeletal, Fractures, Compressions, Bisphosphonates
Medical subject headings
Fractures, Bone

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • zoledronic acidDrug

    Also called Zometa

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

  • denosumabBiological

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

Study groups in NCT00321620
Study groupRoleWhat they receive
zoledronic acidActive comparatorNot described
Receives: Drug: zoledronic acid
denosumabExperimentalNot described
Receives: Biological: denosumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 40.5 months

Secondary outcomes (2)

  1. Time to the First On-Study SRE (Superiority)

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

    Measured: Up to 40.5 months

  2. Time to the First-And-Subsequent On-Study SRE

    Time to the first-and-subsequent on-study skeletal-related event (SRE), analyzed for superiority of denosumab using multiple event analysis, 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.

    Measured: Up to 40.5 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 May 2006 (estimated)
  2. Study start1 Apr 2006
  3. Primary completion1 Oct 2009
  4. Study completion24 Feb 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,904 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00321620
Sponsor's protocol ID
20050103
Status last verified
Aug 2018
First submitted
2 May 2006
Last updated
29 Aug 2018
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 21353695

  • 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.

    PubMed 25425475

  • 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.

    PubMed 25449207

  • 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.

    PubMed 33270906

  • 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.

    PubMed 26335402

  • 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.

    PubMed 26093811

  • 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.

    PubMed 24722180

  • 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.

    PubMed 23975226

  • 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.

    PubMed 22975218

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing zoledronic acid and denosumab in people with Bone Metastases, run by Amgen.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Mar 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to the First On-Study SRE (Non-inferiority) (time frame: Up to 40.5 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00321620, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2018; AzTrials last refreshed its copy on 8 Nov 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in