Study of Sorafenib and Transarterial Chemoembolization (TACE) to Treat Hepatocellular Carcinoma

Inclusion Criteria

• Unresectable hepatocellular carcinoma (HCC) patients with liver-predominant disease as described in section 5.1, or patients with hepatocellular carcinoma who refuse surgery. No more than 30% of the cohort should have macrovascular invasion and/or asymptomatic extrahepatic disease. Multifocal HCC is acceptable, no diffuse HCC.
• Age > 18 years old
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Childs class of A or B (up to 7) (see Table 5.0)
• Adequate end-organ function as manifested by:
• Absolute neutrophil count of > 1500/mm3 and platelets > 50,000/mm3
• Creatinine ≤ 2.0
• Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) 2.0
• International normalized ratio (INR) 3000 cells/mm3
• Amylase and lipase ≤ 1.5 the upper limit of normal
• Patients who have received previous hepatic surgery , radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), or cryoablation are eligible if target lesion(s) have not been treated and local therapy completed > 6 weeks prior to entry.
• Left ventricular ejection fraction ≥ 45%
• Patients with asymptomatic HIV infection are not eligible
• Willingness of male and female subjects, who are not surgically sterile or post menopausal, to use reliable methods of birth control for the duration of the study and for 30 days after the last dose of study medication.
• Patient must have signed informed consent prior to registration on study.
• Resolution of all acute toxic effects of any prior local treatment to Common Terminology Criteria for Adverse Events (CTCEA) Grade 1 or 0.
• At least one tumor lesion can be accurately measured in at least one dimension according to RECIST. The lesion has not been previously treated with local therapy (such as surgery, radiation therapy, RFA, PEI, or cryoablation) unless it has shown progression in the interim.

Exclusion Criteria

• Patients unable to swallow oral medications
• Prior embolization, systemic or radiation therapy for HCC (liver)
• Tumor burden in the liver exceeding 70%.
• Complete occlusion of the entire portal venous system
• Ascites refractory to diuretic therapy (minimal or trace on imaging is acceptable)
• Previous or concurrent cancer that is distinct in primary site or histology from HCC, except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis, and T1). Any cancer curatively treated > 3 years prior is permitted.
• Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry
• History of bleeding within the past 4 weeks (unless deemed by PI as clinically insignificant, for ex., a brief episode of epistaxis)
• Any contraindication to doxorubicin administration
• Evidence of severe or uncontrolled systemic diseases,
• Congestive cardiac failure > New York Heart Association (NYHA) class 2, myocardial ischemia within 6 months, active coronary artery disease, cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin, unstable angina, or laboratory finding that in the view of the investigator makes it undesirable for the patient to participate in the trial
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• History of stroke or transient ischemic attack within 6 months prior to study enrollment
• Inadequately controlled hypertension (defined as systolic blood pressure of 150/100 mmHg on antihypertensive medications) (patients with treated hypertension are eligible)
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection, peripheral vascular disease)
• History of organ allograft
• Presence of grade > 2 hepatic encephalopathy (see Appendix D)
• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an additional experimental drug
• Evidence of bleeding diathesis or coagulopathy or on warfarin. Note: If a patient has been on coumadin for a