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

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ClinicalTrials.gov Identifier: NCT00974311
Recruitment Status : Completed
First Posted : September 10, 2009
Results First Posted : October 30, 2012
Last Update Posted : March 19, 2018
Sponsor:
Collaborators:
Astellas Pharma Inc
Medivation, Inc.
Information provided by (Responsible Party):
Pfizer

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Castration-Resistant Prostate Cancer
Interventions: Drug: Enzalutamide
Drug: Placebo

  Participant Flow

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
Participants 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 participant was scheduled to initiate a new systemic anti-neoplastic therapy, death, or withdrawal.
Placebo Participants received placebo tablets orally once a day. Treatment continued until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic 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

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.
Intent-to-treat population (ITT) included all participants who were randomized into the study.

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

Baseline Measures
   Enzalutamide   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 800   399   1199 
Age 
[Units: Participants]
Count of Participants
     
<=18 years      0   0.0%      0   0.0%      0   0.0% 
Between 18 and 65 years      232  29.0%      130  32.6%      362  30.2% 
>=65 years      568  71.0%      269  67.4%      837  69.8% 
Age 
[Units: Years]
Mean (Standard Deviation)
 68.8  (7.96)   68.6  (8.39)   68.7  (8.11) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      0   0.0%      0   0.0%      0   0.0% 
Male      800 100.0%      399 100.0%      1199 100.0% 
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

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:   Percentage of Participants Who Were Responders for Functional Assessment of Cancer Therapy-Prostate (FACT-P)   [ Time Frame: Baseline 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 Participants With Pain Palliation   [ Time Frame: Baseline up to 3 years ]
  Hide Outcome Measure 6

Measure Type Secondary
Measure Title Percentage of Participants With Pain Palliation
Measure Description The proportion of participants with pain palliation was assessed for participants 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 Baseline up to 3 years  

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. Participants 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 participant was scheduled to initiate a new systemic anti-neoplastic therapy, death, or withdrawal.
Placebo Participants received placebo tablets orally once a day. Treatment continued until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death, or withdrawal.

Measured Values
   Enzalutamide   Placebo 
Participants Analyzed 
[Units: Participants]
 49   15 
Percentage of Participants 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 Participants With Pain Palliation
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Cochran-Mantel-Haenszel
P Value [4] 0.0079
Difference in Rate of Pain Palliation [5] 38.2
95% Confidence Interval 19.4 to 57.0
[1] Additional details about the analysis, such as null hypothesis and power calculation:
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[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
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[3] Other relevant method information, such as adjustments or degrees of freedom:
  Stratified by baseline Eastern Cooperative Oncology Group performance status (0–1 vs. 2)
[4] 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.
[5] Other relevant estimation information:
  Confidence Interval based on standard normal approximation



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

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

9.  Secondary:   European Quality of Life Five-Domain (EQ-5D) Scale   [ Time Frame: Week 13 ]

10.  Secondary:   Percentage of Participants With Circulating Tumor Cell (CTC) Conversion   [ Time Frame: Baseline up to 3 years ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

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