Enzalutamide Versus Standard Androgen Deprivation Therapy for the Treatment Hormone Sensitive Prostate Cancer
Condition: Adenocarcinoma of the Prostate; Recurrent Prostate Cancer; Stage III Prostate Cancer; Stage IV Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Enzalutamide; leuprolide acetate; goserelin acetate; histrelin acetate; triptorelin; degarelix
Intervention description: Given PO; Given SC or IM; Given SC or IM; Given SC or IM; Given SC or IM; Given SC or IM
Intervention MeSH terms: Leuprolide; Goserelin; Triptorelin Pamoate; Tryptophan; Androgens
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: Male
Minimum age: 19 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial compares enzalutamide with standard androgen deprivation
      therapy in reducing incidence of metabolic syndrome in patients with prostate cancer that has
      spread to other places in the body. Metabolic syndrome is defined as changes in cholesterol,
      blood pressure, circulating sugar levels, and body weight. Previous studies have shown that
      patients with prostate cancer, who have been treated with standard medical therapy that
      lowers testosterone levels, have an increased risk of these changes. Hormone therapy using
      enzalutamide may fight prostate cancer by blocking the use of testosterone by the tumor cells
      instead of lowering testosterone levels. It is not yet known whether prostate cancer patients
      who receive enzalutamide will have reduced incidence of metabolic syndrome than patients who
      receive standard androgen deprivation therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically proven adenocarcinoma of the prostate; if pathology is
             unavailable, the principal investigator (PI) may also make a determination of prostate
             cancer based on unequivocal clinic data

          -  Patients with advanced prostate cancer suitable for systemic treatment defined as:
             having metastatic disease, a biochemical relapse after primary therapy, or patients in
             whom primary therapy is not appropriate or feasible; patients without metastatic
             disease will need evaluation for local therapy and deemed inappropriate or have
             refused this treatment option

          -  Eastern Cooperative Oncology Group (ECOG) 0-2

          -  Age > 18 years

          -  Must use a condom if having sex with a pregnant woman

          -  A male patient and his female partner who is of childbearing potential must use 2
             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

          -  Life expectancy estimated at > 12 months

          -  Ability to understand and willingness to provide written informed consent document

        Exclusion Criteria:

          -  A history of androgen deprivation therapy; patients receiving hormonal therapy in the
             adjuvant and/or neoadjuvant setting must have discontinued therapy at least 6 months
             prior to day 1 of treatment AND have a serum testosterone level >= 50 ng/dL AND cannot
             have received more than 18 months of previous ADT

          -  A history of orchiectomy

          -  Previous androgen blockade (e.g. antiandrogens) in the last 3 months

          -  Patients already meeting the criteria for metabolic syndrome as defined by the Adult
             Treatment Panel III Criteria which requires 3/5 parameters encompassing glucose
             control, blood pressure, lipids and waist circumference; patients with 2 of the
             parameters at baseline will be allowed enrollment provided that one of those risk
             factors is hypertension (>= 130/>= 85 mm Hg)

          -  Baseline hypogonadism as defined as a testosterone < 50 ng/dL

          -  PSA < 0.5 ng/dL

          -  Serum vitamin D 25, hydroxy (OH) < 12 ng/mL

          -  Active hepatitis C virus

          -  Use of corticosteroids as defined by a daily dose of prednisone (or equivalent) of 5
             mg or greater for more than 1 month continuously within 3 months of screening

          -  Corrected calcium > 10.6 mg/dL

          -  Absolute neutrophil count < 1500/uL

          -  Platelet count < 100,000/uL

          -  Hemoglobin < 9 g/dL

          -  Total bilirubin >= 1.5 x upper limit of normal (ULN) (unless documented Gilbert's)

          -  Alanine aminotransferase or aspartate aminotransferase >= 2.5 x ULN

          -  Creatinine > 2 mg/dL

          -  Clinically significant cardiovascular disease as evidenced by: myocardial infarction
             within 6 months of screening; uncontrolled angina within 3 months of screening; New
             York Heart Association (NYHA) class 3 or 4 congestive heart failure; clinically
             significant ventricular arrhythmia; Mobitz II/2nd degree/or 3rd degree heart block
             without a pacemaker in place; uncontrolled hypertension (HTN) (systolic > 180 mmHg or
             diastolic > 105 mmHg at screening)

          -  Previous exposure to enzalutamide

          -  Use of an investigational therapeutic within 30 days

          -  History of gastrointestinal disorders (medical disorders or extensive surgery) that
             may interfere with the absorption of the study agent

          -  Known or suspected brain metastasis or active leptomeningeal disease

          -  History of seizure or any condition that may predispose to seizure (e.g., prior
             cortical stroke, significant brain trauma) at any time in the past; also, history of
             loss of consciousness or transient ischemic attack within 12 months of day 1 visit

          -  Have any condition that, in the opinion of the investigator, would compromise the
             well-being of the subject or the study or prevent the subject from meeting or
             performing study requirements