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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00286091
First received: February 2, 2006
Last updated: May 20, 2015
Last verified: May 2015
Results First Received: March 25, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition: Hormone Refractory Prostate Cancer
Interventions: Biological: Denosumab
Biological: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Eligible subjects were men ≥ 18 years old with histologically-confirmed, castrate-resistant prostate cancer who were chemically or surgically castrated. The first patient was enrolled into the study on 03 February 2006 and the last patient was enrolled on 23 July 2008.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were randomized to denosumab or placebo in the double-blind treatment phase. All participants undergoing scheduled assessments were offered open-label denosumab for up to 3 years in the open-label extension phase. Three enrolled patients were excluded from all datasets per ethics committee’s instructions due to eligibility violations.

Reporting Groups
  Description
Placebo Participants received placebo subcutaneous injection every 4 weeks (Q4W) in the double-blind treatment phase. Participants then received open-label denosumab 120 mg by subcutaneous injecton once every 4 weeks for up to 3 years in the open-label extension phase.
Denosumab Participants received 120 mg densumab administered by subcutaneous injection every 4 weeks in the double-blind treatment phase. Participants then received open-label denosumab 120 mg by subcutaneous injecton once every 4 weeks for up to 3 years in the open-label extension phase.

Participant Flow for 2 periods

Period 1:   Double-blind Treatment Phase
    Placebo     Denosumab  
STARTED     716     716  
Received Treatment     709 [1]   716  
On Study at Primary Data Analysis Cutoff     164 [2]   174 [2]
COMPLETED     132 [3]   123 [3]
NOT COMPLETED     584     593  
Withdrawal by Subject                 103                 113  
Protocol-Specified Criteria                 307                 269  
Death                 58                 65  
Adverse Event                 28                 40  
Disease Progression                 22                 35  
Other                 25                 33  
Administrative Decision                 20                 21  
Noncompliance                 8                 8  
Lost to Follow-up                 11                 4  
Protocol Deviation                 1                 3  
Ineligibility Determined                 1                 2  
[1] 4 participants received ≥ 1 dose of denosumab in error
[2] Primary analysis cut-off date was 30 July 2010
[3] On study through blinded treatment cutoff date of 09 January 2011

Period 2:   Open-label Treatment Phase
    Placebo     Denosumab  
STARTED     110 [1]   104 [1]
Received Treatment     109     101  
COMPLETED     33 [2]   33 [2]
NOT COMPLETED     77     71  
Physician Decision                 24                 21  
Adverse Event                 5                 16  
Other                 11                 11  
Withdrawal by Subject                 14                 10  
Death                 10                 7  
Disease Progression                 9                 3  
Noncompliance                 3                 1  
Lost to Follow-up                 0                 1  
Protocol-specified Criteria                 1                 0  
Missing End of Study Information                 0                 1  
[1] Participants in the Czech Republic and UK are reported separately (Study 20080585; NCT01824342)
[2] Completed 3 years of open-label treatment



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo Participants received placebo subcutaneous injection every 4 weeks (Q4W) in the double-blind treatment phase. Participants then received open-label denosumab 120 mg by subcutaneous injecton once every 4 weeks for up to 3 years in the open-label extension phase.
Denosumab Participants received 120 mg densumab administered by subcutaneous injection every 4 weeks in the double-blind treatment phase. Participants then received open-label denosumab 120 mg by subcutaneous injecton once every 4 weeks for up to 3 years in the open-label extension phase.
Total Total of all reporting groups

Baseline Measures
    Placebo     Denosumab     Total  
Number of Participants  
[units: participants]
  716     716     1432  
Age  
[units: years]
Mean (Standard Deviation)
  73.2  (8.3)     73.2  (8.8)     73.2  (8.6)  
Gender  
[units: participants]
     
Female     0     0     0  
Male     716     716     1432  
Race/Ethnicity, Customized  
[units: participants]
     
White or Caucasian     604     606     1210  
Black or African American     35     41     76  
Hispanic or Latino     37     32     69  
Asian     18     17     35  
Japanese     2     0     2  
American Indian or Alaska Native     2     0     2  
Native Hawaiian or Other Pacific Islander     1     0     1  
Other     17     18     35  
Unknown     0     2     2  
Eastern Cooperative Oncology Group (ECOG)Pperformance Status [1]
[units: participants]
     
Grade 0     514     505     1019  
Grade 1     199     210     409  
Grade 2     3     1     4  
Grade 3     0     0     0  
Grade 4     0     0     0  
Prostate-Specific Antigen (PSA) Doubling Time  
[units: participants]
     
≤ 10 months     580     574     1154  
> 10 months     136     142     278  
Prostate-Specific Antigen (PSA) ≥ 8.0 ng/mL  
[units: participants]
     
Yes     471     473     944  
No     245     243     488  
Prior Chemotherapy Regimens  
[units: participants]
     
Yes     54     63     117  
No     662     653     1315  
[1] A scale to assess a patient's disease status. 0 = Fully active, able to carry out all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature; 2 = Ambulatory and capable of all self care, unable to carry out any work activities. Up and about > 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair > 50% of waking hours; 4 = Completely disabled, confined to bed or chair; 5 = Dead.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Bone Metastasis-free Survival   [ Time Frame: 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. ]

2.  Secondary:   Time to First Bone Metastasis   [ Time Frame: 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. ]

3.  Secondary:   Overall Survival   [ Time Frame: 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. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Amgen Inc.
phone: 866-572-6436


Publications:

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00286091     History of Changes
Other Study ID Numbers: 20050147
Study First Received: February 2, 2006
Results First Received: March 25, 2015
Last Updated: May 20, 2015
Health Authority: Australia: Therapeutic Goods Administration
Canada: Health Canada
EU: EMEA
United States: Food and Drug Administration