Enzalutamide/Leuprolide +/- Abiraterone/Pred in Prostate
Condition: Prostate Adenocarcinoma; Prostate Cancer; High Risk Prostate Cancer
MeSH terms: Prostatic Neoplasms; Adenocarcinoma
Intervention: Enzalutamide; Abiraterone Acetate; Prednisone; Leuprolide Acetate
Intervention description: 160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Can be taken with or without food.; 1000 mg (four 250 mg tablets), oral, once daily, 28 days (4 weeks) 6 cycles maximum. No food should be consumed for at least two hours before the dose and for at least one hour after the dose.; 5 mg, oral, once daily, 28 days (4 weeks) 6 cycles maximum.Take with food, preferred to be taken in the morning .; Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.
Intervention MeSH terms: Prednisone; Leuprolide; Abiraterone Acetate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 75.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: prostate adenocarcinoma; advanced prostate cancer; high risk prostate cancer

Summary:

      This study is comparing the effectiveness of enzalutamide with or without abiraterone acetate
      for men with high-risk, localized prostate cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male greater than or equal 18 years of age.

          -  Histologically confirmed adenocarcinoma of the prostate without histological variants
             (including overt neuroendocrine differentiation, small cell neuroendocrine carcinoma
             features, sarcomatoid features, pure ductal adenocarcinoma, squamous or transitional
             cell carcinoma).

          -  Must have tissue available from the pre-treatment diagnostic biopsy (tissue blocks if
             possible; if not possible, 10 unstained slides from each positive core sample for a
             total of 30 slides).

          -  Must have three core biopsies involved with cancer (a minimum of 6 core biopsies must
             be obtained). Prostate biopsy must be within three months from screening.

          -  Participants must have the following features:

               -  Intermediate-risk disease defined as Gleason 4+3=7 disease OR

               -  High-risk disease defined as Gleason 8-10 OR PSA > 20 ng/dL OR T3 disease (by
                  prostate MRI)

          -  No evidence of metastatic or nodal disease as determined by radionuclide bone scans
             CT/MRI.

          -  Participants must be candidates for RP and considered surgically resectable by
             urologic evaluation.

          -  ECOG performance status 0 to 1 (Appendix A).

          -  Participants must have normal organ and marrow function as defined below:

               -  WBC ≥ 3,000/mcL

               -  ANC ≥ 1,500/mcL

               -  Platelets ≥ 100,000/mcL

               -  Serum potassium ≥ 3.5 mmol/L

               -  AST, ALT, and total bilirubin ≤ 1.5 x Institutional ULN

               -  Calculated creatinine clearance ≥ 60 mL/min

               -  PTT ≤ 60, INR ≤ 1.5 x Institutional ULN unless on warfarin therapy (investigator
                  would need to determine if safe for participant to stop warfarin prior to biopsy
                  and warfarin therapy)

               -  Controlled blood pressure defined as a systolic blood pressure ≤ 140 mmHg and
                  diastolic blood pressure ≤ 90 mmHg on no more than three anti-hypertensive
                  agents. Drug formulations containing two or more anti-hypertensive agents will be
                  counted based on the number of active agents in each formulation.

        Exclusion Criteria:

          -  Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens
             (including first-generation antiandrogens, enzalutamide, ARN-509 and others), CYP17
             inhibitors (including abiraterone, TAK-700, galeterone, ketoconazole, and others),
             estrogens, LHRH agonist/antagonists. Prior therapy with 5α-reductace inhibitors is
             allowed. LHRH therapy allowed if begun within 4 weeks of day 1.

          -  Prior chemotherapy, radiation therapy, or immunotherapy for prostate cancer.

          -  Prior systemic treatment with an azole drug within four weeks of screening visit.

          -  Hypogonadism or severe androgen deficiency as defined by screening serum testosterone
             < 200 ng/dL.

          -  Clinically significant cardiovascular disease including:

          -  Acute coronary syndrome within 6 months of screening visit;

               -  Hypotension defined as a systolic blood pressure < 86 mmHg;

               -  Bradycardia defined as a heart rate of < 50 beats per minute, unless
                  pharmaceutically induced and thus reversible (i.e. beta blockers);

               -  Uncontrolled angina (requiring escalating doses of nitrates) within 3 months of
                  screening visit;

               -  Congestive heart failure NYHA Class III or IV or subjects with a history of
                  congestive heart failure NYHA Class III or IV, unless screening ECHO results in
                  left ventricular ejection fraction that ≥ 45%;

               -  History of clinically significant ventricular arrhythmias (e.g. ventricular
                  tachycardia, ventricular fibrillation, torsades de pointes);

               -  Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on
                  screening EKG > 470 msec;

               -  History of Mobitz II second degree or third degree heart block without a
                  permanent pacemaker in place;

          -  History of seizure or any condition or concurrent medication that may predispose to
             seizure.

          -  Thromboembolism within 6 months of screening visit.

          -  Severe hepatic impairment (Child-Pugh Class C).

          -  Active or symptomatic viral hepatitis or chronic liver disease.

          -  History of pituitary or adrenal dysfunction.

          -  GI disorders which may interfere with the absorption of the study drug.

          -  Pre-existing condition that warrants long-term corticosteroid use.

          -  Concomitant use of medications that may alter pharmacokinetics of abiraterone or
             enzalutamide.

          -  Individuals with a history of a different malignancy are ineligible except for the
             following circumstances: 1) individuals with a history of other malignancies are
             eligible if they have been disease-free for at least 5 years and are deemed by the
             investigator to be at low risk for recurrence of that malignancy, or 2) individuals
             with the following cancers are eligible if diagnosed and treated within the past 5
             years: non-muscle invasive bladder cancer, basal cell or squamous cell carcinoma of
             the skin.

          -  Major surgery or radiation therapy within 30 days of screening.