A Study of Enzalutamide Versus Bicalutamide in Castrate Men With Metastatic Prostate Cancer
Condition: Prostatic Neoplasms
MeSH terms: Prostatic Neoplasms
Intervention: enzalutamide; bicalutamide
Intervention description: capsules; tablets
Intervention MeSH terms: Bicalutamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 375.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic; MDV3100; Prostate; progressive; Cancer; enzalutamide

Summary:

      The purpose of this study was to determine the efficacy and safety of oral enzalutamide
      compared to bicalutamide in castrate men with metastatic prostate cancer who have progressed
      while on Luteinizing Hormone Receptor Hormone (LHRH) agonist/antagonist or after receiving a
      bilateral orchiectomy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed adenocarcinoma of the prostate without neuroendocrine
             differentiation or small cell features

          -  Ongoing androgen deprivation therapy with a Luteinizing Hormone Receptor Hormone
             (LHRH) agonist or antagonist at a stable dose and schedule within 4 weeks of
             randomization or bilateral orchiectomy (i.e., surgical or medical castration)

          -  Metastatic disease documented by one of the following:

               -  At least two bone lesions on bone scan, or

               -  Soft tissue disease documented by computed tomography (CT)/ magnetic resonance
                  imaging (MRI), or

               -  Unequivocal pelvic adenopathy short axis > 2.0 cm in diameter by CT/MRI

          -  Progressive disease at study entry defined as one or more of the following three
             criteria occurring in the setting of castrate levels of testosterone:

               -  Prostate Specific Antigen (PSA) progression defined by a minimum of three rising
                  PSA levels with an interval of ≥ 1 week between each determination. The PSA value
                  should be ≥ 2 µg/L (2 ng/mL);

               -  Soft tissue disease progression defined by Response Evaluation Criteria in Solid
                  Tumors (RECIST) 1.1;

               -  Bone disease progression defined by two or more new lesions on bone scan

          -  Asymptomatic or mildly symptomatic from prostate cancer (i.e. the score on the Brief
             Pain Inventory-Short Form (BPI-SF) Question #3 must be < 4); no use of opiate
             analgesics for prostate cancer-related pain currently or anytime within 4 weeks prior
             to randomization

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, including
             subjects with decreased performance status not attributed to progressive and
             symptomatic prostate cancer

          -  Estimated life expectancy of ≥ 12 months

          -  Able to swallow the study drug and comply with study requirements

          -  A male subject and his female spouse/partner who is of childbearing potential must use
             two acceptable methods of birth control (one of which must include a condom as a
             barrier method of contraception) starting at Screening and continuing throughout the
             study period, and for 3 months after final study drug administration. Two acceptable
             forms of birth control include:

               1. Condom (barrier method of contraception), AND

               2. In addition to a condom, one of the following acceptable forms of contraception
                  is required:

                    -  Established use of oral, injected or implanted hormonal methods of
                       contraception.

                    -  Placement of an intrauterine device (IUD) or intrauterine system (IUS).

                    -  Barrier methods of contraception: Occlusive cap (diaphragm or cervical/vault
                       caps) with spermicidal foam/gel/film/cream/suppository.

                    -  Tubal ligation for at least 6 months prior to Screening

                    -  Vasectomy or other surgical castration at least 6 months prior to Screening

        Exclusion Criteria:

          -  Prior cytotoxic chemotherapy for prostate cancer

          -  Severe concurrent disease, infection, or comorbidity that would make the subject
             inappropriate for enrollment

          -  Known or suspected brain and/or skull metastasis or active epidural disease

          -  History of another malignancy within the previous 5 years other than curatively
             treated non-melanomatous skin cancer

          -  Current or prior treatment with estrogens and/or drugs with anti-androgenic properties
             such as spironolactone > 50 mg/day, or progestational agents for the treatment of
             prostate cancer within 6 months prior to randomization

          -  Current or prior use of ketoconazole for the treatment of prostate cancer

          -  Use of antiandrogens within 6 weeks prior to randomization

          -  Documented prior disease progression while receiving antiandrogens. Disease
             progression defined as PSA progression, radiographic progression and/or clinical
             deterioration.

          -  Current or prior treatment with 5-α reductase inhibitors or anabolic steroids within 6
             months prior to randomization

          -  Prior use of systemic glucocorticoids (the equivalent of 10 mg of prednisone) within 3
             months prior to randomization or expectation of their use during the study

          -  Radiation therapy to bone lesions or prostatic bed within 4 weeks prior to
             randomization

          -  Major surgery within 2 months prior to randomization

          -  History of seizure including febrile seizure or any condition that may predispose to
             seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss
             of consciousness requiring hospitalization). Also, current or prior treatment with
             anti-epileptic medications for the treatment of seizures or history of loss of
             consciousness or transient ischemic attack within 12 months prior to randomization

          -  Clinically significant cardiovascular disease including myocardial infarction within
             past six months or uncontrolled angina within past three months