Clinical trial NCT00321620: Study of Denosumab vs. Zoledronic Acid to Treat Bone Metastases in Men With Hormone-refractory Prostate Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bone Metastases
Keywords: Bone metastases
Hormone-refractory prostate cancer
Skeletal
Fractures
Compressions
Bisphosphonates
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2006-05-04
Enrollment: 1904
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

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

Primary outcomes:
measure: Time to the First On-Study SRE (Non-inferiority)
timeFrame: Up to 40.5 months
Secondary outcomes:
measure: Time to the First On-Study SRE (Superiority)
timeFrame: Up to 40.5 months
measure: Time to the First-And-Subsequent On-Study SRE
timeFrame: Up to 40.5 months
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
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.
citation: 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.
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.
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.