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

Bone Metastases Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00321620
• Other study ID #: 20050103
• Status: Completed
• Phase: Phase 3
• Start date: April 1, 2006
• Est. completion date: February 24, 2012

Study information

• Verified date: August 2018
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1904
• Est. completion date: February 24, 2012
• Est. primary completion date: October 1, 2009
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bone Marrow Diseases
• Bone Metastases
• Bone Neoplasms
• Neoplasm Metastasis
• Neoplasms, Second Primary
• Prostatic Neoplasms

Intervention

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

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

References & Publications (3)

Fizazi K, Carducci M, Smith M, Damião 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. — View Citation

Fizazi K, Massard C, Smith M, Rader M, Brown J, Milecki P, Shore N, Oudard S, Karsh L, Carducci M, Damião 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. — View 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. Erratum in: Ann Oncol. 2015 Jun;26(6):1274. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Up to 40.5 months
Secondary	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.	Up to 40.5 months

External Links

•   AmgenTrials clinical trials website