Randomized Phase 1/2 Open-Label Trial of PR104 and Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)

Inclusion Criteria:

* Advanced-stage hepatocellular carcinoma considered non-operable that is suitable for treatment with sorafenib. Subjects who have demonstrated progression following initial surgical or locoregional therapy are eligible
* Confirmed hepatocellular carcinoma by pathological analysis (tissue aspirate or biopsy)
* No previous systemic therapy for hepatocellular carcinoma
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Child-Pugh liver function class A
* Life expectancy of 12 weeks or more
* Adequate hematologic function \[Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L; platelet count ≥100×10\^9 per liter; hemoglobin ≥8.5 g per deciliter maintained in the absence of red blood cell transfusions; and prothrombin time international normalized ratio ≤1.7; or prothrombin time ≤2 seconds above control\]
* Adequate hepatic function (albumin ≥2.8 g per deciliter; total bilirubin ≤2 mg per deciliter \[51.3 μmol per liter\]; and alanine aminotransferase and aspartate aminotransferase ≤5 times the upper limit of the normal range)
* Adequate renal function (serum creatinine ≤1.5 times the upper limit of the normal range or creatinine clearance ≥60 mL/min).
* At least one untreated target lesion that could be measured in one dimension, according to the Response Evaluation Criteria in Solid Tumors (RECIST)
* Concomitant systemic antiviral therapy allowed

Exclusion Criteria:

* Previous molecularly targeted therapies or any other systemic treatment for hepatocellular carcinoma
* Active concomitant malignancy likely to effect any of the primary or secondary outcome measures in the current study
* Women who are pregnant, breast-feeding or planning to become pregnant during the study
* Men or women of reproductive-potential who are unwilling to use an effective method of contraception during the study and for 30 days following the last dose of study medication
* Evidence of a significant medical disorder or laboratory finding that, in the opinion of the Investigator, compromises the subject's safety during study participation such as: uncontrolled infection or infection requiring a concomitant parenteral antibiotic; uncontrolled diabetes; congestive heart failure; myocardial infarction within 6 months of study; chronic renal disease; or coagulopathy (excluding prophylactic anticoagulation)
* Active central nervous system metastatic disease requiring intervention
* Less than four weeks since major surgery
* Known Human Immunodeficiency Virus (HIV) positivity