Clinical trial NCT00286091: Study on Prolonging Bone Metastasis-Free Survival in Men With Hormone Refractory Prostate Cancer
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Phase 3 Study of Denosumab on Prolonging Bone Metastasis-Free Survival in Men With Hormone Refractory Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hormone Refractory Prostate Cancer
Keywords: Hormone refractory prostate cancer
androgen independent
ADT
bone metastasis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2006-02-03
Enrollment: 1435
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to compare the treatment effect of denosumab with placebo on prolonging bone metastasis-free survival in men with hormone refractory (androgen independent) prostate cancer who have no bone metastasis at baseline.

Detailed description: Participants were randomized to receive denosumab 120 mg or placebo every 4 weeks (Q4W) until approximately 660 participants developed bone metastasis or died and the primary efficacy and safety analyses were completed.

All participants undergoing scheduled assessments were offered open-label denosumab 120 mg subcutaneous (SC) until they either developed a bone metastasis, obtained access to commercially available product in this setting, or for up to 3 years, whichever came first. For participants who ended participation before the open-label extension (OLE) phase or withdrew from investigational product during the OLE phase, their survival data was to be collected every 6 months for up to 3 years after their last dose of investigational product.

Participants in the Czech Republic and United Kingdom were enrolled under a separate protocol for the OLE phase per Health Authority request, and are reported separately (Study 20080585; NCT01824342).

Eligibility criteria: Inclusion Criteria:

* men with histologically confirmed prostate cancer
* bilateral orchiectomy at least 6 months before randomization or continuous androgen-deprivation therapy (ADT) with a gonadotropin releasing hormone (GnRH) agonist or antagonist for at least 6 months before randomization
* total testosterone level less than 50 ng/dL,
* hormone refractory (androgen independent) prostate cancer demonstrated during continuous ADT/post-orchiectomy defined as: 3 consecutive prostate-specific antigen (PSA) values with PSA1 \< PSA2 \< PSA3, each PSA value must be separated by at least 2 weeks, PSA2 and PSA3 greater than or equal to 1.0 ng/mL,
* high risk for development of bone metastasis defined as PSA value greater than or equal to 8.0 ng/mL, obtained no more than 3 months before randomization OR PSA doubling time less than or equal to 10.0 months

Exclusion Criteria:

* prior or current evidence of radiographically detectable bone metastasis
* known prior or current evidence of any metastatic involvement of distant organs (lymph node metastases in any region is acceptable)
* prior or current intravenous bisphosphonate administration

Primary outcomes:
measure: Bone Metastasis-free Survival
timeFrame: From the first dose of investigational product to the primary data cutoff date of 30 July 2010; median time on study was approximately 20 months.
Secondary outcomes:
measure: Time to First Bone Metastasis
timeFrame: From the first dose of investigational product to the primary data cutoff date of 30 July 2010; median time on study was approximately 20 months.
measure: Overall Survival
timeFrame: From the first dose of investigational product to the primary data cutoff date of 30 July 2010; median time on study was approximately 20 months.
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Smith MR, Saad F, Coleman R, Shore N, Fizazi K, Tombal B, Miller K, Sieber P, Karsh L, Damiao R, Tammela TL, Egerdie B, Van Poppel H, Chin J, Morote J, Gomez-Veiga F, Borkowski T, Ye Z, Kupic A, Dansey R, Goessl C. Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet. 2012 Jan 7;379(9810):39-46. doi: 10.1016/S0140-6736(11)61226-9. Epub 2011 Nov 15.