Safety and Efficacy Study of MDV3100 in Patients With Castration-Resistant Prostate Cancer Who Have Been Previously Treated With Docetaxel-based Chemotherapy (AFFIRM)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Astellas Pharma Inc
Information provided by (Responsible Party):
Medivation, Inc.
ClinicalTrials.gov Identifier:
NCT00974311
First received: September 9, 2009
Last updated: February 22, 2014
Last verified: February 2014
Results First Received: September 28, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Castration-Resistant Prostate Cancer
Interventions: Drug: Enzalutamide
Drug: 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
Multicenter, global clinical trial

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients were randomized 2:1 to receive either Enzalutamide or placebo

Reporting Groups
  Description
Enzalutamide Participants received 160 mg Enzalutamide orally per day. Treatment continued until unacceptable toxicity, confirmed disease progression and the patient was scheduled to initiate a new systemic antineoplastic therapy, death, or withdrawal.
Placebo Participants received placebo tablets orally once a day. Treatment continued until unacceptable toxicity, confirmed disease progression and the patient was scheduled to initiate a new systemic antineoplastic therapy, death, or withdrawal.

Participant Flow:   Overall Study
    Enzalutamide     Placebo  
STARTED     800     399  
COMPLETED     254 [1]   163 [1]
NOT COMPLETED     546     236  
Lost to Follow-up                 1                 1  
Death                 305                 211  
Withdrawal of consent                 9                 5  
Continuing Treatment                 231                 19  
[1] Indicates participants continuing long-term follow-up as of 25 September 2011.



  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
Enzalutamide Participants received 160 mg Enzalutamide orally per day. Treatment continued until unacceptable toxicity, confirmed disease progression and the patient was scheduled to initiate a new systemic antineoplastic therapy, death, or withdrawal.
Placebo Participants received placebo tablets orally once a day. Treatment continued until unacceptable toxicity, confirmed disease progression and the patient was scheduled to initiate a new systemic antineoplastic therapy, death, or withdrawal.
Total Total of all reporting groups

Baseline Measures
    Enzalutamide     Placebo     Total  
Number of Participants  
[units: participants]
  800     399     1199  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     232     130     362  
>=65 years     568     269     837  
Age  
[units: years]
Mean ± Standard Deviation
  68.8  ± 7.96     68.6  ± 8.39     68.7  ± 8.11  
Gender  
[units: participants]
     
Female     0     0     0  
Male     800     399     1199  
Region of Enrollment  
[units: participants]
     
United States     181     107     288  
Spain     23     13     36  
Austria     15     10     25  
Chile     6     5     11  
United Kingdom     82     50     132  
Italy     20     10     30  
France     193     80     273  
Canada     82     25     107  
Argentina     7     3     10  
Belgium     27     18     45  
Poland     7     4     11  
Australia     60     33     93  
South Africa     3     3     6  
Germany     62     24     86  
Netherlands     32     14     46  



  Outcome Measures
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1.  Primary:   Overall Survival   [ Time Frame: During study period (up to 3 years) ]

2.  Secondary:   Radiographic Progression-free Survival   [ Time Frame: During study period (up to 3 years) ]

3.  Secondary:   Time to First Skeletal-related Event   [ Time Frame: During study period (up to 3 years) ]

4.  Secondary:   Functional Assessment of Cancer Therapy - Prostate (FACT-P)   [ Time Frame: During study period (up to 3 years) ]

5.  Secondary:   Time to Prostate-specific Antigen (PSA) Progression   [ Time Frame: Baseline and at every study visit from week 13 while on study drug (up to 3 years) ]

6.  Secondary:   Percentage of Patients With Pain Palliation   [ Time Frame: During study period (up to 3 years) ]
  Hide Outcome Measure 6

Measure Type Secondary
Measure Title Percentage of Patients With Pain Palliation
Measure Description The proportion of patients with pain palliation was assessed for patients with a stable and sufficient pain burden at study entry. Pain burden was measured by question #3 of the Brief Pain Inventory (Short Form). This scale measures pain on a 0 to 10 scale with 0 indicating no pain and 10 indicating pain as bad as you can imagine. Pain palliation at Week 13 was determined for the proportion of men with baseline bone metastasis(es) who had baseline pain attributable to the metastasis(es). Palliation was defined as ≥ 30% reduction in average pain score at Week 13 compared to baseline without a ≥ 30% increase in analgesic use.
Time Frame During study period (up to 3 years)  
Safety Issue No  

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.
Evaluable ITT Population. Patients with metastatic bone disease at baseline; provided answers to Question #3 of the Brief Pain Inventory – Short Form for a minimum of 4 out of 7 days in the baseline run-in period; stable baseline pain; stable analgesic use; and had an average pain score during the baseline run-in period of ≥ 4.

Reporting Groups
  Description
Enzalutamide Participants received 160 mg Enzalutamide orally per day. Treatment continued until unacceptable toxicity, confirmed disease progression and the patient was scheduled to initiate a new systemic antineoplastic therapy, death, or withdrawal.
Placebo Participants received placebo tablets orally once a day. Treatment continued until unacceptable toxicity, confirmed disease progression and the patient was scheduled to initiate a new systemic antineoplastic therapy, death, or withdrawal.

Measured Values
    Enzalutamide     Placebo  
Number of Participants Analyzed  
[units: participants]
  49     15  
Percentage of Patients With Pain Palliation  
[units: Percentage¬†of¬†Participants]
Number ( 95% Confidence Interval )
  44.9  
  ( 30.7 to 59.8 )  
  6.7  
  ( 0.2 to 31.9 )  


Statistical Analysis 1 for Percentage of Patients With Pain Palliation
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.0079
Difference in Rate of Pain Palliation [4] 38.2
95% Confidence Interval ( 19.4 to 57.0 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Stratified by baseline Eastern Cooperative Oncology Group performance status (0–1 vs. 2)
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  Confidence Interval based on standard normal approximation



7.  Secondary:   Percentage of Patients With Prostate Specific Antigen (PSA) Response   [ Time Frame: During study period (up to 3 years) ]

8.  Secondary:   Percentage of Patients With Soft-tissue Objective Response   [ Time Frame: During study period (up to 3 years) ]

9.  Secondary:   European Quality of Life Five-Domain Scale (EQ-5D)   [ Time Frame: At Week 13 visit ]
Results not yet posted.   Anticipated Posting Date:   12/2013   Safety Issue:   No

10.  Secondary:   Circulating Tumor Cell (CTC) Conversion Rate   [ Time Frame: During study period (up to 3 years) ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No


  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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