Enzalutamide Versus Standard Androgen Deprivation Therapy for the Treatment Hormone Sensitive Prostate Cancer

PRIMARY OBJECTIVES:

I. To determine the incidence of metabolic syndrome within 12 months, as defined by the Adult
Treatment Panel III, in patients treated with enzalutamide compared to standard androgen
deprivation therapy.

SECONDARY OBJECTIVES:

I. To determine the incidence of metabolic syndrome within 6 months, as defined by the Adult
Treatment Panel III, in patients treated with enzalutamide compared to standard androgen
deprivation therapy.

II. To assess bone health, as measured by a dual-energy x-ray absorptiometry (DXA) scanner.

III. To assess body composition (sarcopenic obesity), as measured by a DXA scanner.

IV. To assess quality of life (QOL), as measured by the Functional Assessment of Cancer
Therapy-Prostate (FACT-P) and Sexual Health Inventory in Men (SHIM).

V. To assess time to prostate-specific antigen (PSA) progression and time to radiographic
progression.

VI. To assess the incidence of developing individual risk factors, or components, which
comprise metabolic syndrome.

VII. To assess the change in high-sensitivity C-reactive protein (hs-CRP) as a marker of
inflammation.

VIII. To assess the safety and tolerance of enzalutamide or androgen deprivation therapy
(ADT).

IX. To assess the change in physical function as measured by the Short Physical Performance
Battery (SPPB).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive enzalutamide orally (PO) once daily (QD) for 12 months in the absence
of disease progression or unacceptable toxicity.

ARM II: Patients receive standard of care ADT comprising one of the following at the
discretion of the treating physician: leuprolide acetate, goserelin acetate, histrelin
acetate, triptorelin, or degarelix subcutaneously (SC) or intramuscularly (IM) for 12 months
in the absence of disease progression or unacceptable toxicity. Patients may also choose to
undergo surgical castration as an alternative form of ADT.

After completion of study treatment, patients are followed up at 30 days.

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