A Study of Apalutamide (ARN-509) in Men With Non-Metastatic Castration-Resistant Prostate Cancer
Condition: Prostatic Neoplasms
MeSH terms: Prostatic Neoplasms
Intervention: Apalutamide; Placebo
Intervention description: 240 mg tablets administered by mouth on a continuous once daily dosing regimen; Matched placebo tablets administered by mouth on a continuous once daily dosing regimen
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 1207.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Prostate neoplasms; Prostate cancer; Castration-resistant prostate cancer; Non-metastatic castration-resistant prostate cancer; ARN-509; Apalutamide

Summary:

      The purpose of this study is to evaluate the efficacy and safety of apalutamide in adult men
      with high-risk non-metastatic castration-resistant prostate cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed adenocarcinoma of the prostate without
             neuroendocrine differentiation or small cell features with high risk for development
             of metastases, defined as prostate-specific antigen doubling time (PSADT) less than or
             equal to (<=) 10 months. PSADT is calculated using at least 3 prostate-specific
             antigen (PSA) values obtained during continuous ADT (androgen deprivation therapy)

          -  Castration-resistant prostate cancer demonstrated during continuous ADT, defined as 3
             PSA rises, at least 1 week apart, with the last PSA greater than (>) 2 nanogram per
             milliliter (ng/mL)

          -  Maintain castrate levels of testosterone within 4 weeks prior to randomization and
             throughout the study

          -  Patients currently receiving bone loss prevention treatment with bone-sparing agents
             must be on stable doses for at least 4 weeks prior to randomization

          -  Patients who received a first generation anti-androgen (for example, bicalutamide,
             flutamide, nilutamide) must have at least a 4-week washout prior to randomization AND
             must show continuing disease (PSA) progression (an increase in PSA) after washout

          -  At least 4 weeks must have elapsed from the use of 5-alpha reductase inhibitors,
             estrogens, and any other anti-cancer therapy prior to randomization

          -  At least 4 weeks must have elapsed from major surgery or radiation therapy prior to
             randomization

          -  Eastern Cooperative Oncology Group Performance Status 0 or 1

          -  Resolution of all acute toxic effects of prior therapy or surgical procedure to Grade
             <= 1 or baseline prior to randomization

          -  Adequate organ function according to protocol-defined criteria

          -  Administration of growth factors or blood transfusions will not be allowed within 4
             weeks of the hematology labs required to confirm eligibility

        Exclusion Criteria:

          -  Presence of confirmed distant metastases, including central nervous system and
             vertebral or meningeal involvement

          -  Symptomatic local or regional disease requiring medical intervention

          -  Prior treatment with second generation anti-androgens

          -  Prior treatment with CYP17 inhibitors

          -  Prior treatment with radiopharmaceutical agents, or any other investigational agent
             for non-metastatic castration-resistant prostate cancer

          -  Prior chemotherapy for prostate cancer except if administered in the
             adjuvant/neoadjuvant setting

          -  History of seizure or condition that may pre-dispose to seizure

          -  Concurrent therapy with protocol-defined excluded medications

          -  History or evidence of any of the following conditions: any prior malignancy (other
             than adequately treated basal cell or squamous cell skin cancer, superficial bladder
             cancer, or any other cancer in situ currently in complete remission) within 5 years
             prior to randomization; severe/unstable angina, myocardial infarction, symptomatic
             congestive heart failure, arterial or venous thromboembolic events, or clinically
             significant ventricular arrhythmias within 6 months prior to randomization;
             uncontrolled hypertension; gastrointestinal disorder affecting absorption; active
             infection; and, any other condition that, in the opinion of the investigator, would
             impair the patient's ability to comply with study procedures