Safety and Efficacy Study of Enzalutamide Versus Bicalutamide in Men With Prostate Cancer

The purpose of this study is to determine the safety and efficacy of enzalutamide vs bicalutamide in asymptomatic or mildly symptomatic patients with prostate cancer who have disease progression despite primary androgen deprivation therapy.

This study is a multicenter phase 2, randomized, double-blind, efficacy and safety study of enzalutamide (160 mg/day) vs. bicalutamide (50 mg/day) in patients with recurrent prostate cancer who have serologic and/or radiographic disease progression despite primary androgen deprivation therapy.

Throughout the study, safety and tolerability will be assessed by the recording of adverse events, monitoring of vital signs, physical examinations, and safety laboratory evaluations.

Following study unblinding, study patients receiving enzalutamide or bicalutamide at the time of unblinding and qualifying patients randomized to bicalutamide who discontinued prior to unblinding will be offered the opportunity to receive open label enzalutamide treatment.

Eligibility Criteria:
Inclusion Criteria:

* Males age 18 or older;
* Histologically or cytologically confirmed adenocarcinoma of the prostate;
* Ongoing androgen deprivation therapy;
* Serum testosterone level ≤ 50 ng/dL (1.73 nmol/L) at the Screening visit;
* Progressive disease at study entry defined by prostate-specific antigen (PSA) progression and/or radiographic progression that occurred while the patient was on primary androgen deprivation therapy;
* Asymptomatic or mildly symptomatic from prostate cancer;
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
* Estimated life expectancy of ≥ 12 months;
* Able to swallow the study drug and comply with study requirements.

Exclusion Criteria:

* Severe concurrent disease, infection, or co-morbidity;
* Known or suspected brain metastasis or active leptomeningeal disease;
* History of another invasive malignancy within the previous 5 years other than treated non-melanomatous skin cancer and American Joint Committee on Cancer (AJCC) Stage 0 or Stage 1 cancers that have a remote probability of recurrence;
* Absolute neutrophil count \< 1,500/µL, or platelet count \< 100,000/µL, or hemoglobin \< 9 g/dL at the Screening visit;
* Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 times the upper limit of normal (ULN) at the Screening visit;
* Creatinine \> 2 mg/dL at the Screening visit;
* Albumin \< 3.0 g/dL at the Screening visit;
* History of seizure or any condition that may predispose to seizure;
* Clinically significant cardiovascular disease;
* Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within last 3 months);
* Major surgery within 4 weeks of enrollment;
* Use of opiate analgesics for pain from prostate cancer within 4 weeks of enrollment;
* Radiation therapy for treatment of the primary tumor within 3 weeks of enrollment;
* Prior radiation or radionuclide therapy for treatment of distant metastases;
* Prior ketoconazole, abiraterone, or cytotoxic chemotherapy for prostate cancer;
* Treatment with hormonal therapy or biologic therapy for prostate cancer within 4 weeks of enrollment;
* Use of antiandrogens within 4 weeks prior to enrollment;
* Prior disease progression, as assessed by the Investigator, while receiving bicalutamide;
* Participation in a previous clinical trial of enzalutamide or an investigational agent that inhibits the androgen receptor or androgen synthesis (patients who received placebo are acceptable);
* Use of an investigational agent within 4 weeks of enrollment;
* Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids for prostate cancer within 4 weeks of enrollment;
* Any condition or reason that, in the opinion of the Investigator, interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of safety data.

Open-Label Treatment Period:

Inclusion Criteria:

* Received randomized double blind treatment in MDV3100-09 as follows:

  * Randomized to enzalutamide and receiving enzalutamide at the time of study unblinding;
  * Randomized to bicalutamide and receiving bicalutamide at the time of study unblinding;
  * Randomized to bicalutamide and discontinued bicalutamide before study unblinding;
* Willing to maintain androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) agonist/antagonist or has had a bilateral orchiectomy.

Exclusion Criteria:

* Is currently or has taken commercially available enzalutamide (Xtandi) prior to participation in this open-label extension;
* Discontinued enzalutamide during the double-blind portion of the study prior to unblinding;
* Has any clinically significant cardiovascular, dermatologic, endocrine, gastrointestinal, hematologic, hepatic, infectious, metabolic, neurologic, psychiatric, psychologic, pulmonary, or renal disorder or any other condition, including excessive alcohol or drug abuse, or secondary malignancy, that may interfere with study participation in the opinion of the investigator or medical monitor;
* Has a current or previously treated brain metastasis or leptomeningeal disease;
* Has a history of seizure or any condition that may predispose to seizure (eg, prior cortical stroke or significant brain trauma);
* Has a history of loss of consciousness or transient ischemic attack within 12 months of open label day 1;
* Has taken cytotoxic chemotherapy or investigational therapy within 4 weeks before enrollment (open label day 1).