Denosumab for Prolonging Bone Metastasis-Free Survival in Men With Hormone-Refractory Prostate Cancer

Study Overview
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Brief Summary
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This is a multi-national, multi-center, open-label, single-arm extension study for the prolongation of bone metastasis-free survival in men with hormone-refractory (androgen independent) prostate cancer. Patients currently participating in the phase 3 study 20050147 (NCT00286091) will be offered this study if a positive benefit:risk compared with placebo is determined in the 20050147 study. The primary endpoint of the 20050147 study is bone metastases-free survival determined by the time to first occurrence of bone metastases (either symptomatic or asymptomatic) or death from any cause. Participants will receive open-label denosumab administered once every 4 weeks (Q4W) subcutaneously (SC) until they developed a bone metastasis or for up to 3 years, whichever comes first.

Official Title
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An Open Label, Single Arm, Extension Study to Evaluate the Long Term Safety of Denosumab for Prolonging Bone Metastasis-Free Survival in Men With Hormone-Refractory Prostate Cancer

Conditions
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Castrate-resistant Prostate Cancer

Intervention / Treatment
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* Biological: Denosumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects currently undergoing every 4 weeks scheduled assessments in the phase 3 study 20050147 Subjects must sign the informed consent before any study specific procedures are performed Exclusion Criteria: Developed sensitivity to mammalian cell derived drug products during the 20050147 study Currently receiving any unapproved investigational product other than denosumab Any disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or comply with study procedures

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Denosumab<br>Participants received denosumab 120 mg subcutaneously every 4 weeks for up to 3 years in this open-label extension study. | Biological: Denosumab<br>* Administered by subcutaneous injection<br>* Other names: XGEVA®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (AEs) and Deaths | A serious adverse event is defined as an adverse event that meets at least one of the following serious criteria: • fatal, • life threatening, • requires in-patient hospitalization or prolongation of existing hospitalization, • results in persistent or significant disability/incapacity, • congenital anomaly/birth defect, and/or • other significant medical hazard. The adverse event severity grading scale used was the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, according to the following: Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE; Grade 5 = Death related to AE. The investigator assessed whether each adverse event was possibly related to the investigational product (IP). | From the first dose of open-label denosumab until 4 weeks after the last; maximum time on study was 37 months. Follow-up survival information was collected for up to 3 years after the last dose of blinded investigation product in the 20050147 study. | 
| Percent Change From Baseline in Laboratory Values |  | Baseline and Week 49 | 
| Number of Participants With Anti-denosumab Neutralizing Antibody Formation |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | A scale used to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. 0 = Fully active, able to carry out all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work); 2 = Ambulatory and capable of all self care, but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled. Cannot carry out any self-care. Totally confined to bed or chair; 5 = Dead. | Baseline and Week 49 |