Enzalutamide in Patients With High-risk Prostate Cancer
Condition: Adenocarcinoma of the Prostate
MeSH terms: Prostatic Neoplasms; Adenocarcinoma
Intervention: enzalutamide
Intervention description: oral therapy with enzalutamide at 160mg (4 capsules) orally once daily (QD).
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Prostate cancer; adenocarcinoma of the prostate; Enzalutamide

Summary:

      The purpose of this study is to see how long it takes for prostate cancer to come back in
      patients who have had surgery to remove their prostate gland (radical prostatectomy), while
      being treated with enzalutamide (formerly known as MDV3100).

      Enzalutamide is known as an androgen-receptor signaling inhibitor, which means that it blocks
      activity of the male hormone, testosterone. Most prostate cancers are dependent on
      testosterone for growth. In this study, patients will take enzalutamide after surgery to see
      if it keeps their cancer from coming back.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Understand and voluntarily sign an informed consent form.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          -  Histologically confirmed adenocarcinoma of the prostate.

          -  Patients must have undergone a Radical Prostatectomy (any surgical technique is
             permitted) within 3 months from study entry and have high-risk disease define by any
             of the following:

               -  Pathological stage T3a, T3b, T4 (any grade or iPSA)

               -  Gleason' sum ≥ 8 (any stage or iPSA)

               -  Initial Pre-operative PSA ≥ 20ng/mL (any GS or pT stage)

               -  Any stage/PSA/Gleason patients with a 35% or greater chance of biochemical
                  failure at 5 years based on Kattan's nomogram
                  http://nomograms.mskcc.org/Prostate/PostRadicalProstatectomy.

               -  Patients with Lymph node (LN) positive disease, regardless of iPSA, pT stage or
                  GS provided their post-operative PSA 6-8 weeks after surgery is ≤ 0.4ng/mL.
                  (Lymph node dissection is desired but not mandated)

          -  Able to swallow the study drug and comply with study requirements.

          -  Patients must have normal organ and marrow function as defined below:

               -  Testosterone ≥ 50 ng/dL per laboratory reference range

               -  Baseline Post-RP PSA ≤ 0.4

               -  Hemoglobin ≥ 10.0 g/dL independent of transfusion

               -  Absolute neutrophil count ≥1,500/mcL

               -  Platelet count ≥100,000/ìL

               -  Serum albumin ≥ 3.5 g/dL

               -  Serum potassium ≥ 3.5 mmol/L

               -  Liver function: serum bilirubin < 1.5 x ULN (except for patients with documented
                  Gilbert's disease) and AST or ALT < 2.5 x ULN

        Exclusion Criteria:

          -  Severe concurrent disease, infection, or co-morbidity that, in the judgment of the
             investigator, would make the patient inappropriate for enrollment

          -  Prior radiotherapy to the prostate or pelvis (related to prostate cancer). Concurrent
             adjuvant radiation therapy is permitted once patient has been enrolled on trial.

          -  Prior use of Abiraterone acetate or cytotoxic chemotherapy for prostate cancer

          -  Prior androgen deprivation with Luteinizing hormone-releasing hormone (LHRH) is
             permitted provided that testosterone levels prior to study entry have recovered to
             normal limits per reference laboratory.

          -  No prior anti-androgen therapy (bicalutamide, flutamide or Nilutamide) is permitted

          -  Prior use of 5-alpha reductase inhibitors is permitted provided such medications were
             stopped 7-14 days prior to 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 greater
             than the equivalent of 10 mg of prednisone per day within 2 weeks of enrollment

          -  Active unresolved infection

          -  Known history of central nervous system (CNS) metastases

          -  Patients must have no known history of HIV

          -  Evidence of metastatic disease as evidenced by a CT or MRI of abdomen and pelvis
             and/or whole body bone scan (WBS). To be done prior to treatment start and up to 4
             months prior to radical prostatectomy date.

          -  History of seizure or any condition that may predispose to seizure (e.g., prior
             cortical stroke, significant brain trauma). Also, history of loss of consciousness or
             transient ischemic attack within 12 months of enrollment.

          -  Clinically significant cardiovascular disease including:

               -  Myocardial infarction within 6 months prior to Screening;

               -  Uncontrolled angina within 3 months prior to Screening;

               -  Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or
                  patients with history of congestive heart failure NYHA class 3 or 4 in the past,
                  unless a screening echocardiogram (ECHO) or multi-gated acquisition scan (MUGA)
                  performed within 3 months results in a left ventricular ejection fraction that is
                  ≥ 45%

               -  History of clinically significant ventricular arrhythmias (e.g., ventricular
                  tachycardia, ventricular fibrillation, torsades de pointes)

               -  History of Mobitz II second degree or third degree heart block without a
                  permanent pacemaker in place

               -  Hypotension as indicated by systolic blood pressure < 86 mmHg at the Screening
                  visit

               -  Bradycardia as indicated by a heart rate of < 50 beats per minute on the
                  Screening ECG

               -  Uncontrolled hypertension as indicated by systolic blood pressure > 170 mmHg or
                  diastolic blood pressure > 105 mmHg at the Screening visit

          -  Gastrointestinal disorder affecting absorption (e.g., Gastrectomy, active peptic ulcer
             disease within last 3 months)

          -  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.

          -  The effects of enzalutamide on the developing human fetus at the recommended
             therapeutic doses are unknown. Thus, men must agree to use adequate contraception
             (barrier method of birth control or abstinence) prior to study entry, for the duration
             of study participation, and for 6 months after the usage of enzalutamide. Should the
             patient's partner become pregnant or suspect she is pregnant while the patient is
             participating in this study, the patient should inform his treating physician
             immediately.