Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

This Phase I trial is studying the side effects and best dose of sorafenib in treating patients with locally advanced or metastatic liver cancer and cirrhosis.

Eligibility

You must be at least 18 years old to participate in this study.

Disease Characteristics

• Hepatocellular carcinoma (HCC) according to tissue histology
• Local advanced or metastatic disease or not eligible for surgical resection or immediate liver transplantation
• Child-Pugh class B cirrhosis
• Moderate hepatic dysfunction (bilirubin ≤ three times upper limit of normal) or severe hepatic dysfunction (bilirubin > three times but ≤ six times upper limit of normal)
• No known brain metastasis unless the metastasis has been stable for more than three months

Patient Characteristics

• ECOG performance status is zero to one
• Life expectancy is greater than 12 weeks 
• Hemoglobin > 9.0 g/dL 
• ANC > 1,000/mm^3 
• Platelet count > 45,000/mm^3 
• ALT and AST < seven times ULN 
• INR < 2.0 
• Creatine < 1.7 times ULN OR creatinine clearance > 50 mL/min 
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for approximately two weeks after completion of study treatment

Exclusion Criteria

Patients will be excluded from the trial if they meet any of the following criteria:

• History of uncontrolled seizures, CNS disorders, or psychiatric disability that, in the opinion of the investigator, is clinically significant, precludes giving informed consent, or interferes with compliance of oral drug intake 
• Other concurrent active malignancy 
• Active clinically serious infection with a CTCAE grade greater than two
• Hypersensitivity to sorafenib tosylate or to any of the excipients 
• Known or suspected allergy to sorafenib tosylate or to any agent given in the course of this study
• NYHA class III or IV congestive heart failure 
• Unstable angina or new onset angina (i.e., within the past three months) 
• Myocardial infarction within the past six months 
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy 
• Uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or diastolic BP > 90 mm Hg, despite optimal medical management 
• Thrombolic or embolic events (e.g., cerebrovascular accident, including transient ischemic attacks) within the past six months 
• Pulmonary hemorrhage/bleeding event greater than CTCAE grade two within the past four weeks 
• Hemorrhage/bleeding event greater than CTCAE grade three within the past four weeks 
• Variceal bleeding within the past 90 days
• Grade two or three esophageal varices 
• Evidence or history of bleeding diathesis or coagulopathy 
• Significant traumatic injury within the past four weeks 
• Serious non-healing wound, ulcer, or bone fracture 
• Serious uncontrolled medical condition (e.g., uncontrolled ascites or encephalopathy) that, in the opinion of the investigator, may compromise study participation 
• Condition that would impair the patient's ability to swallow whole pills 
• Malabsorption problems
• Active drug or alcohol abuse 

Prior or Concurrent Therapy Requirements

• Systemic chemotherapy
• Hepatic artery infusion of chemotherapy 
• Chemoembolization 
• Radioembolization 
• Ablation 
• At least four weeks since prior embolization, resection, or ablation 
• No prior RAF/MEK/ERK-targeting therapy or VEGF-targeting therapy 
• More than four weeks since prior participation in an investigational drug study 
• More than four weeks since prior major surgery or open biopsy 
• No concurrent chronic anticoagulation other than one mg of warfarin per day for central venous catheter patency
• No concurrent St. John's wort or rifampin

For more information, contact the clinical research coordinator at 919-668-1861.