The purpose of this research study is to determine if sorafenib improves the effectiveness of a procedure called radiofrequency ablation (RFA) for the treatment of hepatocellular cancer (HCC). Radiofrequency ablation has been used to treat many types of tumors, including hepatocellular cancers. During RFA a needle is inserted into the tumor tissue and heat is used to kill the tumor cells. Sorafenib has been approved by the FDA for the treatment of hepatocellular cancer that cannot be treated with surgery. Pre-clinical data suggests that sorafenib may improve the efficacy of RFA.

Hepatocellular cancer (HCC) has a poor prognosis with increasing mortality in the United States. Because HCC generally develops in patients with underlying liver disease, resection is often not possible. Liver transplant improves survival for HCC patients but given the national organ donor shortage often patients have to wait a considerable time for transplant. Liver-directed therapies such as radiofrequency ablation (RFA) remain important tools to control tumor growth and to potentially "bridge" patients to liver transplant. However, liver-directed therapies for HCC tumors greater than 3cm in size are suboptimal, leaving a critical unmet need.

Antiangiogenic systemic agents, such as oral sorafenib, reduce tumor blood flow and have been shown to improve RFA efficacy in animal and in computer models.

Inclusion Criteria:

• Confirmed hepatocellular cancer (HCC) by pathology or by NCCN imaging guidelines
• All HCC stages are allowed. May be a liver transplant candidate.
• At least one tumor (index tumor) accurately measured as 3.5-7cm in diameter (long and short axis diameter to be recorded, but only one needs to meet this criteria) on baseline imaging.
• No prior therapy for the index tumor
• No prior systemic treatment for HCC within 4 weeks and no prior anti-VEGF therapy within 8 weeks of study entry.
• Life expectancy > 8 weeks.
• ECOG >=0 or 1
• RFA clinically indicated for index tumor.
• Acceptable overall RFA and anesthesia risk.
• Adequate bone marrow, liver and renal function: Hemoglobin >9.0 g/dl; Absolute neutrophil count (ANC)>1,500/mm3; Platelet count correctable to >50,000/mm3; compensated liver function (Child-Turcotte-Pugh A, B7 or B8); Creatinine <1.5 times ULN; INR correctable to <1.5.
• Ability to take oral medication and no evidence of impaired absorption.

Exclusion Criteria

• Urgent treatment of the index tumor anticipated.
• Participants who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Participants currently receiving any other study agents.
• Known brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib.
• Participants receiving medications or substances that are inducers of CYP3A4 (rifampicin, St. John's wort, phenytoin, carbamazepine, phenobarbital and dexamethasone) or that are metabolized/eliminated by predominantly UGT1A1 pathway or by CYP2B6 and CYP2C8.
• Decompensated liver disease
• Uncontrolled hypertension
• Thrombolic or embolic events within the past 6 months.
• Hemorrhage/bleeding event within 4 weeks
• Serious non-healing wound, ulcer, or bone fracture.
• Evidence of severe or uncorrectable bleeding diathesis or coagulopathy
• Major surgery, open biopsy or significant traumatic injury within 4 weeks of study entry.
• Contraindication to or inability to undergo the RFA procedure,
• Contraindication to or inability to undergo imaging with MRI
• Uncontrolled intercurrent illness
• Individuals with a history of a different malignancy unless disease-free for at least 5 years and are deemed by the Investigator to be at low risk for recurrence. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
• HIV-positive individuals on combination antiretroviral therapy

For additional inclusion/exclusion criteria details contact Study Site.

The analysis population is comprised of all enrolled participants.

Adverse events were collected on treatment days 1-10 and the day 40 follow-up visit.

Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term. The analysis population is all treated patients (n=1 dropped out before starting treatment.

This study is limited by small sample size.