CRPC2

Medivation, Inc. Medivation is now a wholly owned subsidiary of Pfizer Inc.

525 Market St, San Francisco, United States, 94105

Clinical Trial Disclosure, Medivation, Inc. , 1 415-543-3470, trialdisclosure@medivation.com

Clinical Trial Disclosure, Medivation, Inc. , 1 415-543-3470, trialdisclosure@medivation.com

No

No

No

Interim

25 Sep 2011

Yes

25 Sep 2011

No

The purpose of this study was to determine the benefit of enzalutamide as compared to placebo as assessed by overall survival in patients with progressive castration-resistant prostate cancer whose disease was progressing after 1 or 2 prior chemotherapy regimens, at least 1 of which was docetaxel-based.

This study was conducted in conformance with the principles of the Declaration of Helsinki or with the laws and regulations of the country in which the research was conducted, whichever provided greater protection of the individual. In addition, the study was conducted using Good Clinical Practice (GCP) according to International Council on Harmonisation (ICH) guidelines. Specifically, this study was based on adequately performed laboratory and animal experimentation; the study was conducted under a protocol reviewed and approved by an IRB/IEC; the study was conducted by scientifically and medically qualified persons; the benefits of the study were in proportion to the risks; the rights and welfare of the patients were respected; the physicians conducting the study did not find the hazards to outweigh the potential benefits.

22 Sep 2009

Yes

Yes

Netherlands: 46

Poland: 11

Spain: 36

United Kingdom: 132

Austria: 25

Belgium: 45

France: 273

Germany: 86

Italy: 30

United States: 288

Chile: 11

Canada: 107

Argentina: 10

Australia: 93

South Africa: 6

1199

684

0

0

0

0

0

0

362

819

18

Overall Study (overall period)

Randomised - controlled

Yes

Enzalutamide

Capsule

Oral use

Patients received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth. Treatment continued until unacceptable toxicity, confirmed disease progression and the patient was scheduled to initiate a new systemic antineoplastic therapy, death, or withdrawal.

Placebo

Capsule

Oral use

Patients received placebo 160 mg, administered as four 40-mg capsules, once per day by mouth. Treatment continued until unacceptable toxicity, confirmed disease progression and the patient was scheduled to initiate a new systemic antineoplastic therapy, death, or withdrawal.

Enzalutamide

Placebo

Enzalutamide

Placebo

Intent-to-treat (ITT)

All patients who were randomized into the study.

Evaluable FACT-P

All patients who were part of the ITT Population and had a global FACT-P score at baseline and at least 1 post-baseline assessment.

Evaluable Pain Palliation

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.

Overall survival is defined as time from randomization to death due to any cause. The duration of overall survival was right-censored for patients who were lost to follow-up since randomization or not known to have died at the data analysis cutoff date (this included patients who were known to have died after the data analysis cutoff date). '99999' indicates that the upper limit of the 95% confidence interval was not calculable because an insufficient number of patients reached the event at the final time point for assessment.

Primary

During study period (up to 3 years)

Enzalutamide v Placebo

1199

Pre-specified

0.63

2-sided

Radiographic progression-free survival was defined as time from randomization to the earliest objective evidence of radiographic progression or death due to any cause. Patients were assessed for objective disease progression at regularly scheduled visits. The consensus guidelines of the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) were taken into consideration for the determination of disease progression. Radiographic disease progression was defined by RECIST 1.1 for soft tissue disease, or the appearance of two or more new bone lesions on bone scan, as per the PCWG2 guidelines. Progression at the first scheduled reassessment at Week 13 required a confirmatory scan 6 or more weeks later. Patients who did not reach the endpoint were right censored at their last assessment.

Secondary

During study period (up to 3 years)

Enzalutamide v Placebo

1199

Pre-specified

0.4

2-sided

The time to first skeletal-related event was defined as time from randomization to the occurrence of the first skeletal-related event. Patients were assessed for skeletal-related events at regularly scheduled visits. A skeletal-related event was defined as radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression, or change of antineoplastic therapy to treat bone pain. Patients who did not reach the endpoint were right censored at their last assessment or for patients with no post-baseline assessment for skeletal-related event, at date of randomization..

Secondary

During study period (up to 3 years)

Enzalutamide v Placebo

1199

Pre-specified

0.688

2-sided

The FACT-P questionnaire is a 39-item questionnaire consisting of 5 domains; “physical well-being,” “social/family well-being,” “emotional well-being,” “functional well-being,” and “additional concerns” (consisting of items relating to prostate cancer and its treatment). Each item can be answered on a scale of 0–4. The sum of scores on all 5 domains constitutes the FACT-P. Patients were defined as having a quality of life response if they had a 10-point improvement in their global FACT-P score, as compared with baseline, on two consecutive measurements obtained at least 3 weeks apart.

Secondary

During study period (up to 3 years)

Enzalutamide v Placebo

908

Pre-specified

24.9

2-sided

Time to PSA progression was defined as time from randomization to PSA progression. Patients who did not reach the endpoint were right censored at their last assessment or for patients with no post-baseline PSA assessment, date of randomization. For patients with PSA declines at Week 13, the PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir was documented, which was confirmed by a second consecutive value obtained 3 or more weeks later (required only if PSA progression did not occur at last PSA assessment). For patients with no PSA declines at Week 13, PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the baseline was documented, which was confirmed by a second consecutive value 3 or more weeks later (required only if PSA progression did not occur at last PSA assessment).

Secondary

Baseline and at every study visit from week 13 while on study drug (up to 3 years)

Enzalutamide v Placebo

1199

Pre-specified

0.248

2-sided

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.

Secondary

During study period (up to 3 years)

Enzalutamide v Placebo

64

Pre-specified

38.2

2-sided

Patients were evaluable for PSA response rate if they had a PSA level measured at baseline and at least 1 post-baseline assessment. PSA responses required confirmation with a subsequent assessment that was conducted at least 3 weeks later.

Secondary

During study period (up to 3 years)

The best overall soft tissue objective response was defined as partial response [PR] or complete response [CR] while on study treatment based on investigator assessments of target, nontarget, and new lesions using RECIST 1.1. Soft tissue was assessed by CT or MRI at regularly scheduled visits. Only patients with measurable soft tissue disease (ie, at least 1 target lesion identified per RECIST 1.1) at screening are included in this analysis. All percentages are based on number of patients with measurable soft tissue disease at screening in each treatment group.

Secondary

During study period (up to 3 years)

The period of time after the first dose of study drug, and continuing up to 30 days after the patient's last dose of study drug, or prior to initiation of another systemic antineoplastic therapy, whichever occurred first.

12.0

Enzalutamide

Placebo