A Randomized Study of Enzalutamide in Patients With Localized Prostate Cancer Undergoing Active Surveillance
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Enzalutamide; Active Surveillance
Intervention description: Oral
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 227.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Therapeutic Cancer Progression; Pathological Cancer Progression; Enzalutamide; Prostate Cancer; Active surveillance

Summary:

      The primary purpose of this study was to compare the time to prostate cancer progression
      (pathological or therapeutic progression) between patients treated with enzalutamide versus
      patients undergoing active surveillance.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically proven adenocarcinoma of the prostate diagnosed (with ≥10 core biopsy)
             within 6 months of screening. The biopsy that was used for this diagnosis must be
             submitted for central pathology review.

          -  Prostate cancer categorized (as determined by central pathology review) as low risk is
             defined as T1c-T2a, PSA<10, N0, M0 (or presumed N0, M0 if CT/bone scan not done due to
             low risk of metastases), GS ≤ 6, ECOG status ≤2 and estimated life expectancy >5 years
             OR intermediate risk is defined as T2b-T2c, PSA<20, N0, M0 (or presumed N0, M0 if
             CT/bone scan not done), GS ≤7 (3+4 pattern only), ECOG status ≤ 2 and estimated life
             expectancy > 5 years. Prostate cancer categorized (as determined by central pathology
             review) to the very low risk category (T1c, GS ≤6, PSA <10 ng/mL, fewer than 3
             prostate biopsy cores positive,

             ≤50% cancer in any core, PSA density <0.15 ng/mL/g) is not included.

          -  Ability to swallow study drugs and to comply with study requirements throughout the
             study

          -  Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written
             Informed Consent and privacy language as per national regulations must be obtained
             from the subject or legally authorized representative prior to any study-related
             procedures

          -  Throughout study, male subject and a female partner who is of childbearing potential
             must use two acceptable methods of birth control (one of which must include a condom
             barrier method of contraception) starting at screening and continuing throughout the
             study period and for three months after the final study drug administration. Two
             acceptable methods of birth control thus include the following:

               1. Condom (barrier method of contraception) AND

               2. One of the following is required:

             i. Established use of oral, injected or implanted hormonal methods of contraception by
             the female partner; ii. Placement of an intrauterine device or intrauterine system by
             the female partner; iii. Additional barrier method: Occlusive cap (diaphragm or
             cervical/vault caps) with spermicidal foam / gel / film / cream / suppository by the
             female partner; iv. Tubal ligation in the female partner.

          -  Must not donate sperm starting at screening throughout the study period and for 90
             days after the final study drug administration.

        Exclusion Criteria:

          -  Prior radiotherapy, surgery, chemotherapy, or hormonal therapy for prostate cancer

          -  Very low risk category (T1c, GS ≤6, PSA <10 ng/mL, fewer than 3 prostate biopsy cores
             positive, ≤50% cancer in any core, PSA density <0.15 ng/mL/g)

          -  Prior transurethral resection of the prostate or prior transurethral microwave
             thermotherapy of the prostate

          -  Use of oral glucocorticoids within 1 month of screening

          -  Use of 5 alpha reductase inhibitor within 1 month of screening or total use, within
             the last two years prior to screening, of >3 months

          -  Presence of metastatic disease

          -  History of seizure or any condition that may predispose to seizures at any time in the
             past. History of loss of consciousness or transient ischemic attack within 12 months
             of screening

          -  Absolute neutrophil count < 1,500/μL, platelet count < 100,000/μL, or hemoglobin < 6.2
             mmol/L (10 g/dL) at screening

          -  Total bilirubin >1.5 times the upper limit of normal (ULN) or alanine aminotransferase
             (ALT) or aspartate aminotransferase (AST) ≥ 2.5 X ULN at screening

          -  Creatinine > 177 μmol/L (> 2 mg/dL) at screening

          -  Albumin < 30 g/L (3.0 g/dL) at screening

          -  Major surgery within 4 weeks prior to Randomization Visit

          -  Clinically significant cardiovascular disease including:

               1. Myocardial infarction or uncontrolled angina within 6 months

               2. Congestive heart failure New York Heart Association (NYHA) class 3 or 4

               3. History of clinically significant ventricular arrhythmias

               4. History of Mobitz II second degree or third degree heart block without a
                  permanent pacemaker in place

               5. Hypotension as indicated by systolic blood pressure < 86 millimeters of mercury
                  (mm Hg) at screening

               6. Bradycardia as indicated by a heart rate of < 45 beats per minute on the
                  screening electrocardiogram (ECG) and on physical examination

               7. Uncontrolled hypertension as indicated by at least 2 consecutive measurements of
                  a resting systolic blood pressure > 170 mmHg or diastolic blood pressure > 105
                  mmHg at the Screening Visit

          -  Known hypersensitivity to enzalutamide or any of its components.

          -  Subject has received investigational therapy within 28 days or 5 half lives, whichever
             is longer, prior to screening