A Study to Assess the Efficacy and Safety of Enzalutamide in Subjects With Advanced Hepatocellular Carcinoma

Inclusion Criteria: * Subject is ≥ 18 years of age or is considered an adult according to local regulation at the time of signing informed consent. * Subject has a documented diagnosis of advanced HCC of any etiology. * Subject has BCLC stage B or C. * Subject's lesions are not amenable to local therapies which may be beneficial, such as transarterial chemoembolization (TACE), radiofrequency ablation, radiotherapy, etc., and the subject is not a candidate for any curative treatments such as resection or liver transplant. * Subject has hepatic function status of Child Pugh Class A at Screening. * Subject received prior systemic treatment for HCC with sorafenib or other anti-VEGF therapy and had confirmed disease progression or discontinued treatment due to a drug-related toxicity. Subject may have received 1 line of systemic therapy before or after sorafenib/anti-VEGF treatment. * Subject has adequately recovered from toxicities due to prior HCC therapy to ≤ grade 1. * Subject has an ECOG performance status ≤ 1 at Screening and on Day 1. * Subject has available formalin-fixed, paraffin-embedded tumor specimen with adequate viable tumor cells in a tissue block or unstained serial slides accompanied by an associated pathology report prior to enrollment. Archival or fresh biopsy tissue is required. * Subject has an estimated life expectancy of at least 3 months on Day 1, in the opinion of the investigator. * Female subject is either: * Not of childbearing potential: postmenopausal (defined as no spontaneous menses for at least 12 consecutive months prior to Screening with follicle-stimulating hormone \[FSH\] \> 40 IU/L for women \< 55 years of age at Screening), or documented to be surgically sterile or status posthysterectomy (at least 1 month prior to Screening). * Or, if of childbearing potential: must have a negative urine pregnancy test at Screening and on Day 1 before the first dose of study drug is administered, and must use 2 acceptable methods of birth control\* if sexually active from Screening through 3 months after the last dose of study drug. * Sexually active male subject and his female partner who is of childbearing potential must use 2 acceptable methods of birth control from Screening through 3 months after the last dose of study drug. \* Two acceptable methods of birth control are as follows: * Condom (barrier method of contraception); AND * One of the following is required: Placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female subject or female partner of a male subject; Additional barrier method: contraceptive sponge or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository by the female subject or female partner of a male subject. For male subject or male partner of female subject, vasectomy or other procedure resulting in infertility (e.g., bilateral orchiectomy) performed at least 6 months before Screening. Tubal ligation in the female partner of a male subject performed at least 6 months before Screening. Established and ongoing use of oral, injected, or implanted hormonal contraceptive by female partner of a male subject. * Female subject must not be breastfeeding at Screening or during the study period and for 3 months after final study drug administration. * Subject must agree not to donate sperm or ova from first dose of study drug through 3 months after the last dose of study drug. * Throughout the study, male subject must use a condom if having sex with a pregnant woman. * Subject must be able to swallow study drug and comply with study requirements. * Subject agrees not to participate in another interventional study while on treatment. * Received double-blind enzalutamide study treatment during the main study. Exclusion Criteria: * Subject has a severe concurrent disease, infection or comorbidity that, in the judgment of the investigator, would make the subject inappropriate for enrollment. * Subject has fibrolamellar variant of HCC. * Subject has status of Child-Pugh Class B or C at Screening. * Subject has a history of organ allograft including liver transplant. * Subject has uncontrolled symptomatic ascites. * Subject has known or suspected brain metastasis or active leptomeningeal disease. * Subject has a history of a non-HCC malignancy with the following exceptions: * The subject with a previous history of a noninvasive carcinoma is eligible if in the opinion of the investigator he/she has had successful curative treatment any time prior to Screening and requires no further therapy for the malignancy. * For all other malignancies, the subject is eligible if he/she has undergone potentially curative therapy and has been considered disease free for at least 3 years prior to Screening. * Subject has inadequate marrow, hepatic, and/or renal function at the Screening Visit defined as: * Absolute neutrophil count \< 1.5 x109/L (\< 1500 cells/mm3) * Platelet count \< 50 x109/L (\< 50,000 cells/mm3) * Hemoglobin \< 8.5 g/dL (\< 5.3 mmol/L) * International normalized ratio \> 1.7 * Albumin \< 2.8 g/dL (\< 28 g/L) * Total bilirubin (TBL) \> 2 x ULN * AST or ALT \> 5 x ULN * Creatinine \> 1.5 x ULN * Note: Transfusions/infusions to meet eligibility criteria are not allowed but if in the opinion of the Principal Investigator, it is beneficial, the patient may be rescreened after receiving one of these procedures. * Subject has a history of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma, encephalopathy within 3 months of Day 1). * Subject has a history of bleeding esophageal varices within 3 months before the Day 1 visit. * Subject has a history of loss of consciousness or transient ischemic attack within 12 months before the Day 1 visit. * Subject has clinically significant cardiovascular disease including: * Myocardial infarction within 6 months before the Day 1 visit. * Uncontrolled angina within 6 months before the Day 1 visit. * Congestive heart failure New York Heart Association (NYHA) Class III or IV or history of congestive heart failure NYHA Class III or IV in the past, unless a Screening echocardiogram or multi-gated acquisition scan performed within 3 months before the Day 1 visit reveals a left ventricular ejection fraction that is ≥ 45%. * History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, Torsade 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 on 2 consecutive measurements at the Screening visit. * Bradycardia (in the presence of known cardiovascular disease) as indicated by a heart rate of \< 50 beats per minute on the Screening electrocardiogram (ECG) recording. * Uncontrolled hypertension as indicated by systolic blood pressure \> 170 mmHg or diastolic blood pressure \> 105 mmHg on 2 consecutive measurements at the Screening visit. * Subject has a gastrointestinal disorder affecting absorption. * Subject had previous local therapy (e.g., surgery, radiation therapy, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation) within 14 days prior to Day 1, has not recovered from toxicities from prior local therapy or may require major surgical procedure during the course of the study. * Subject has received chemotherapy, immunotherapy or any other systemic anticancer therapy (including sorafenib) or any other investigational drug within 14 days prior to the Day 1 visit. * Subject has received an agent that either blocks androgen synthesis or targets the AR (e.g., abiraterone acetate, bicalutamide, enzalutamide, ARN-509 or other investigational AR signaling inhibitors). The exception of spironolactone is allowed after Medical Monitor consultation. * Subject has used any of the following within 28 days before the Day 1 visit: * 5-α reductase inhibitors * Systemic androgens and estrogens (vaginal estrogen creams are allowed) * Herbal therapies, with an antitumor effect. * Subject has a known history of positive test for Human Immunodeficiency Virus. * Subject has shown a hypersensitivity reaction to the active pharmaceutical ingredient or any of the enzalutamide capsule components, including caprylocaproyl polyoxylglycerides (Labrasol), butylated hydroxyanisole and butylated hydroxytoluene. * Subject has addictive/substance abuse problems. * Subject has any other condition or reason that, in the opinion of the investigator, interferes with the ability of the subject to participate in the trial, places the subject at undue risk or complicates the interpretation of safety data. * Received double-blind placebo during the main study.