Study of Sorafenib, Gemcitabine, and Cisplatin in Advanced Hepatocellular Carcinoma (HCC)

Inclusion Criteria: * Hepatocellular carcinoma: diagnosed histologically, cytologically, or clinically by a rising AFP \> 500 ng/ml in the setting of cirrhosis and a radiographically compatible lesion. * No prior systemic therapy; local therapy such as chemoembolization, radiofrequency ablation or cryoablation is allowed. * Measurable disease \> 1 cm by CT or MRI. Lesions which have received local therapy do not qualify as measurable target lesions. * Age \> 18 years old * ECOG Performance Status 0 or 1 * Child-Pugh status A and B * Adequate bone marrow, liver and renal function as assessed by the following: * Hemoglobin ≥ 9.0 g/dl * Absolute neutrophil count (ANC) ≥ 1,250/mm3 * Platelet count ≥ 80,000/mm3 * Total bilirubin ≤ 3.0 mg/dl * ALT and AST ≤ 5 times the ULN * Amylase and lipase ≤ 1.5 times ULN * Creatinine ≤ 1.5 times ULN * Resolution of all acute toxic effects of any prior local treatment to CTC Adverse Events grade £1. * Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment * Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least three months after the last administration of sorafenib. * Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures. * INR \< 1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR or PT and PTT should be measured prior to initiation of sorafenib and monitored at Day 1 and Day 8 of each cycle. Exclusion Criteria: * Prior surgery, radiation or local therapy within 4 weeks. * Prior treatment with either sorafenib, gemcitabine, or cisplatin * Cardiac disease: Congestive heart failure \> class II NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months. * Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis. * Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy. * Uncontrolled hypertension defined as sustained systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management. * Known human immunodeficiency virus (HIV) infection * Active clinically serious infection \> CTCAE Grade 2. * Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months. * Serious non-healing wound, ulcer, or bone fracture. * Evidence or history of bleeding diathesis or coagulopathy * Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug. * Use of St. John's Wort or rifampin (rifampicin). * Known or suspected allergy to sorafenib, cisplatin, or gemcitabine. * Any condition that impairs patient's ability to swallow whole pills. * Any malabsorption problem. * Uncontrolled ascites (defined as not easily controlled with diuretic treatment).