Sorafenib Tosylate in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery

PRIMARY OBJECTIVES:

I. To determine whether the proportion of cytotoxic T lymphocytes that are producing granzyme
B (denoted pGrzB) as measured ~28-35 days after initiation of sorafenib (sorafenib tosylate)
therapy correlates with overall survival, defined as the number of months between the start
of sorafenib treatment and death from any cause.

SECONDARY OBJECTIVES:

I. To determine whether higher pGrzB levels will correlate with better sorafenib tolerance,
manifested by fewer dose reductions, dose interruptions and adverse events.

II. To determine whether improved immune function may also result in greater recognition of
hepatitis viral antigens.

OUTLINE:

Patients receive sorafenib tosylate orally (PO) twice daily (BID). Treatment continues in the
absence of disease progression or unacceptable toxicity.

After completion of study, patients are followed up for 30 days or after the 6 month time
point if continuing sorafenib tosylate and then periodically thereafter.

Inclusion Criteria:

- Subject or legal representative must understand the investigational nature of this
study and sign an Independent Ethics Committee/Institutional Review Board approved
written informed consent form prior to receiving any study related procedure

- Outpatients with histologically/cytologically documented or radiographically diagnosed
unresectable hepatocellular carcinoma (HCC) who are candidates for systemic therapy
and for whom a decision to treat with sorafenib has been made; radiographic diagnosis
needs typical findings of HCC by a radiographic method, i.e. on multi-dimensional
dynamic computed tomography (CT), CT hepatic arteriography (CTHA)/CT arterial
portography (CTAP) or magnetic resonance imaging (MRI)

- Patients must have a life expectancy of at least 8 weeks

- Patients must not have any evidence of bleeding diathesis or active gastrointestinal
bleeding

Exclusion Criteria:

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant or nursing female subjects

- Unwilling or unable to follow protocol requirements

- Any condition which in the investigator's opinion deems the subject an unsuitable
candidate to receive study drug

- Patients who have had prior anti-angiogenic therapy, including but not limited to
sorafenib, brivanib, bevacizumab, or sunitinib; prior treatment with liver directed,
ablative or surgical therapies will be permitted as long as there is documented
progression justifying the need for starting sorafenib therapy

- No known contraindications to anti-angiogenics such as severe coronary artery disease,
recent myocardial infarction or stroke within 6 months, bleeding peptic ulcer or
varices within last 3 months, and any other major illness that may jeopardize study
treatment or follow up