Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer

Men starting first line androgen deprivation therapy for metastatic prostate cancer.

Inclusion criteria:

1. Male aged 18 or older with metastatic adenocarcinoma of the prostate

2. Target or non-target lesions according to Response Evaluation Criteria in Solid
Tumours (RECIST) 1.1

3. Adequate bone marrow function: Haemoglobin (Hb) ≥100g/L and White Cell Count (WCC) ≥
4.0 x 109/L and platelets ≥100 x 109/L.

4. Adequate liver function: Alanine transaminase (ALT) < 2 x Upper Limit of Normal (ULN)
and bilirubin < 1.5 x ULN, (or if bilirubin is between 1.5-2 x ULN, they must have a
normal conjugated bilirubin). If liver metastases are present ALT must be < 5 x ULN

5. Adequate renal function: calculated creatinine clearance > 30 ml/min (Cockcroft-Gault)

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Patients with
performance status 2 are only eligible if the decline in performance status is due to
metastatic prostate cancer.

7. Study treatment both planned and able to start within 7 days after randomisation.

8. Willing and able to comply with all study requirements, including treatment and
required assessments

9. Has completed baseline Health-Related Quality of Life (HRQL) questionnaires UNLESS is
unable to complete because of limited literacy or vision

10. Signed, written, informed consent

Exclusion Criteria:

1. Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small
cell components

2. History of

- seizure or any condition that may predispose to seizure (e.g., prior cortical
stroke or significant brain trauma).

- loss of consciousness or transient ischemic attack within 12 months of
randomization

- significant cardiovascular disease within the last 3 months including: myocardial
infarction, unstable angina, congestive heart failure, ongoing arrhythmias of
Grade >2 [National Cancer Institute Common Terminology Criteria for Adverse
Events (CTCAE), version 4.03], thromboembolic events (e.g., deep vein thrombosis,
pulmonary embolism). Chronic stable atrial fibrillation on stable anticoagulant
therapy is allowed.

3. Life expectancy of less than 12 months.

4. History of another malignancy within 5 years prior to randomisation, except for either
non- melanomatous carcinoma of the skin or, adequately treated, non-muscle-invasive
urothelial carcinoma of the bladder (Tis, Ta and low grade T1 tumours).

5. Concurrent illness, including severe infection that might jeopardize the ability of
the patient to undergo the procedures outlined in this protocol with reasonable safety

a. Human Immunodeficiency Virus (HIV)-infection is not an exclusion criterion if it is
controlled with anti-retroviral drugs that are unaffected by concomitant enzalutamide.

6. Presence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule,
including alcohol dependence or drug abuse;

7. Patients who are sexually active and not willing/able to use medically acceptable
forms of barrier contraception.

8. Prior ADT for prostate cancer (including bilateral orchidectomy), except in the
following settings:

- Started less than 12 weeks prior to randomisation AND Prostate Specific Antigen
(PSA) is stable or falling. The 12 weeks starts from whichever of the following
occurs earliest: first dose of oral anti- androgen, LHRHA, or surgical
castration.

- In the adjuvant setting, where the completion of adjuvant hormonal therapy was
more than 12 months prior to randomisation AND the total duration of hormonal
treatment did not exceed 24 months. For depot preparations, hormonal therapy is
deemed to have started with the first dose and to have been completed when the
next dose would otherwise have been due, e.g. 12 weeks after the last dose of
depot goserelin 10.8mg.

9. Prior cytotoxic chemotherapy for prostate cancer, but up to 2 cycles of docetaxel
chemotherapy for metastatic disease is permitted.

10. Participation in other clinical trials of investigational agents for the treatment of
prostate cancer or other diseases.