Inclusion Criteria:

• Subjects must have histologically confirmed advanced or inoperable HCC
• Child-Pugh liver function class A
• Measurable disease with at least one unidimensionally measurable lesion per RECIST guidelines with modifications
• Adequate organ and hematological function
• Men or women greater than or equal to 18 years old
• Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
• Able to tolerate infusions and self-administer oral medications

Exclusion Criteria:

• Any previous systemic chemotherapy for HCC (chemotherapy or targeted therapies)
• Previous surgical resections are allowed if ≥ 30 days elapsed prior to enrollment
• Locoregional therapies (e.g. TACE) are allowed if ≥ 30 days elapsed prior to enrollment provided that subjects either have a target lesion which has not been subjected to local therapy and/or the target lesions(s) within the field of the local therapy has shown an increase of ≥ 20% in size
• History of arterial or venous thromboembolism within 12 months prior to enrollment
• History of clinically significant bleeding within 6 months prior to enrollment including pulmonary hemorrhage, gastroesophageal varices or gross hemoptysis (greater than or equal to ½ teaspoon or 2.5 mL of bright red blood)
• Anticoagulation therapy must be stopped 1 week prior to enrollment except:
• aspirin and anti-platelet agents
• low dose warfarin (i.e. ≤ 1mg daily)
• Concomitant anti-viral therapy is allowed with the exception of interferon alfa or pegylated interferon alfa therapy
• Known ongoing pancreatitis
• Known history of central nervous system metastases
• Clinically significant cardiovascular disease within 12 months prior to enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stent
• Uncontrolled hypertension as defined as diastolic > 90 mmHg OR systolic > 150 mmHg. The use of anti-hypertensive medications to control hypertension is permitted
• Exclude subjects with a history of prior malignancy, except:
• Malignancy treated with curative intent and with no known active disease present for greater than or equal to 3 years before enrollment and felt to be at low risk for recurrence by treating physician
• Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease
• Adequately treated cervical carcinoma in situ without evidence of disease
• Prostatic intraepithelial neoplasia without evidence of prostate cancer
• Other primary solid tumor with no known active disease present that in the opinion of the investigator will not affect patient outcome in the setting of current hepatocellular carcinoma diagnosis
• Non-healing wound, ulcer (including gastrointestinal) or fracture