Study on Prolonging Bone Metastasis-Free Survival in Men With Hormone Refractory Prostate Cancer

Amgen

Status and phase: Completed; Phase 3

Conditions: Hormone Refractory Prostate Cancer

Treatments: Biological: Placebo; Biological: Denosumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00286091

20050147

Details and patient eligibility

About

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.

Full 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).

Enrollment: 1,435 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,435 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants received placebo subcutaneous injections every 4 weeks during the double-blind treatment phase. Participants then received open-label denosumab 120 mg by subcutaneous injection every 4 weeks during the open-label extension phase.

Treatment:

Biological: Placebo

Denosumb

Experimental group

Description:

Participants received 120 mg denosumab administered by subcutaneous injection every 4 weeks during the double-blind treatment phase. Participants then received open-label denosumab 120 mg by subcutaneous injection every 4 weeks during the open-label extension phase.

Treatment:

Biological: Denosumab