A Phase IB Study of Sorafenib for Patient With Locally Advanced or Metastatic Hepatocellular Carcinoma and Child's B Cirrhosis

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of hepatocellular carcinoma (HCC) according to tissue histology* NOTE:
*Recurrence of previously resected HCC does not require tissue confirmation if there
is clear radiographic recurrence, in the opinion of the investigator

- Locally advanced or metastatic disease OR not eligible for surgical resection or
immediate liver transplantation

- Child-Pugh class B cirrhosis

- Moderate hepatic dysfunction (bilirubin ≤ 3 times upper limit of normal [ULN])
OR severe hepatic dysfunction (bilirubin > 3 times but ≤ 6 times ULN)

- No known brain metastasis unless the metastasis has been stable for > 3 months

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- Life expectancy > 12 weeks

- Hemoglobin > 9.0 g/dL

- ANC > 1,000/mm^3

- Platelet count > 45,000/mm^3

- ALT and AST < 7 times ULN

- INR < 2.0

- Creatinine < 1.7 times ULN OR creatinine clearance > 50 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 2 weeks after
completion of study treatment

- No 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

- No other concurrent active malignancy

- No active clinically serious infection > CTCAE grade 2

- No known hypersensitivity to sorafenib tosylate or to any of the excipients

- No known or suspected allergy to sorafenib tosylate or to any agent given in the
course of this study

- No NYHA class III or IV congestive heart failure

- No unstable angina

- No new onset angina (i.e., within the past 3 months)

- No myocardial infarction within the past 6 months

- No cardiac ventricular arrhythmias requiring anti-arrhythmic therapy

- No uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or
diastolic BP > 90 mm Hg, despite optimal medical management

- No thrombolic or embolic events (e.g., cerebrovascular accident, including transient
ischemic attacks) within the past 6 months

- No pulmonary hemorrhage/bleeding event > CTCAE grade 2 within the past 4 weeks

- No other hemorrhage/bleeding event > CTCAE grade 3 within the past 4 weeks

- No variceal bleeding within the past 90 days

- No known grade 2 or 3 esophageal varices

- No evidence or history of bleeding diathesis or coagulopathy

- No significant traumatic injury within the past 4 weeks

- No serious non-healing wound, ulcer, or bone fracture

- No other serious uncontrolled medical condition (e.g., uncontrolled ascites or
encephalopathy) that, in the opinion of the investigator, may compromise study
participation

- No condition that would impair the patient's ability to swallow whole pills

- No malabsorption problem

- No active drug or alcohol abuse

PRIOR CONCURRENT THERAPY:

- No more than one prior therapy including, but not limited to, any of the following:

- Systemic chemotherapy

- Hepatic artery infusion of chemotherapy

- Chemoembolization

- Radioembolization

- Ablation

- At least 4 weeks since prior embolization, resection, or ablation

- No prior RAF/MEK/ERK-targeting therapy or VEGF-targeting therapy

- More than 4 weeks since prior participation in an investigational drug study

- More than 4 weeks since prior major surgery or open biopsy

- No concurrent chronic anticoagulation other than 1 mg of warfarin per day for central
venous catheter patency

- No concurrent St. John's wort or rifampin