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 SolidTumours (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 musthave a normal conjugated bilirubin). If liver metastases are present ALT must be < 5x 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 withperformance status 2 are only eligible if the decline in performance status is dueto 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 andrequired assessments

9. Has completed baseline Health-Related Quality of Life (HRQL) questionnaires UNLESSis 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 smallcell components

2. History of

• seizure or any condition that may predispose to seizure (e.g., prior corticalstroke or significant brain trauma).

• loss of consciousness or transient ischemic attack within 12 months ofrandomization

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

3. Life expectancy of less than 12 months.

4. History of another malignancy within 5 years prior to randomisation, except foreither non- melanomatous carcinoma of the skin or, adequately treated,non-muscle-invasive urothelial carcinoma of the bladder (Tis, Ta and low grade T1tumours).

5. Concurrent illness, including severe infection that might jeopardize the ability ofthe patient to undergo the procedures outlined in this protocol with reasonablesafety a. Human Immunodeficiency Virus (HIV)-infection is not an exclusion criterion if itis controlled with anti-retroviral drugs that are unaffected by concomitantenzalutamide.

6. Presence of any psychological, familial, sociological or geographical conditionpotentially 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 acceptableforms of barrier contraception.

8. Prior ADT for prostate cancer (including bilateral orchidectomy), except in thefollowing 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 followingoccurs earliest: first dose of oral anti- androgen, LHRHA, or surgicalcastration.

• In the adjuvant setting, where the completion of adjuvant hormonal therapy wasmore than 12 months prior to randomisation AND the total duration of hormonaltreatment did not exceed 24 months. For depot preparations, hormonal therapy isdeemed to have started with the first dose and to have been completed when thenext dose would otherwise have been due, e.g. 12 weeks after the last dose ofdepot goserelin 10.8mg.

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

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