Safety and Efficacy Study of Enzalutamide Versus Bicalutamide in Men With Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Enzalutamide; Bicalutamide
Intervention description: 160 mg, daily, by mouth.; 50 mg, daily, by mouth
Intervention MeSH terms: Bicalutamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 396.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: prostate cancer; enzalutamide; MDV3100

Summary:

      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.
    

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).