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 1.7
• Albumin 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 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, enzalut