Study of Enzalutamide With and Without Sorafenib in Advanced Hepatocellular Carcinoma Patients

This is a multicenter, open label, phase I/II study of enzalutamide with or without sorafenib to define the safety, MTD, and pharmacokinetic parameters of each regimen in advanced HCC patients. The study will have 4 parts as indicated in the Study Schema, an enzalutamide dose escalation (Part 1A), a sorafenib and enzalutamide dose escalation (Part 1B), and dose expansion cohorts for the Part 1A and Part 1B MTDs (Part 2). Dose escalation will occur using a standard 3 + 3 design and is described in Section 4.2.1. For Part 2, the enzalutamide expansion cohort (Part 2A), will enroll 10 patients and is exploratory in nature; however, it will allow for acquisition of additional PK sampling at the MTD, for determination of safety and efficacy. The MTD sorafenib and enzalutamide combination expansion (Part 2B) will be designed using a Simon minimax design to formally evaluate the 4-month PFS.