Inclusion Criteria:

- Patients with unresectable BCLC Stage B/C hepatocellular carcinoma that is
biopsy-proven ( histology or cytology from prior tumor biopsy specimen is acceptable)

- Patients without prior systemic treatment ( chemotherapy or molecular targeted
therapy) except prior adjuvant therapy, if given more than 6 months ago

- Patients who had prior local therapy ( TACE; PEI; RFA) more than 4 weeks prior to
study entry

- No radiotherapy within 4 weeks before entry

- Child-Pugh class A only ( Appendix A)

- Age 21 years and older

- ECOG performance status 0 or 1 ( Appendix A)

- Life expectancy > 3 months.

- Patients must have normal organ and marrow function as defined below:

Absolute neutrophil count > 1.5 x 109/L;Platelets> 75 x 109/L; Haemoglobin >
9.0g/dl;Total bilirubin < 51umol/L ( 3 mg /dL); AST(SGOT)/ALT(SGPT) < 5 X institutional
ULN; Creatinine 1.5 ULN; INR <1.7 or prothrombin time ( PT) <4 seconds above
ULN; Left ventricular ejection fraction (LVEF) >50%

- Measurable disease according to RECIST. A lesion which has previously been locally
treated (including TACE or RFA) is eligible as long as there is evidence of disease
progression

- Suitable for oral administration of drug

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Prior systemic therapy including sorafenib or a MEK inhibitor or sunitinib or other
investigational drugs

- Any prior local therapy ( surgery, radiation therapy, hepatic arterial embolization,
or cryoablation) within 4 weeks of study entry.

- Prior liver transplant

- NCI CTCAE grade > 3 hemorrhage within 4 weeks of starting study treatment, or
documented variceal hemorrhage of any grade within 12 months of study entry (as
documented on endoscopy)

- Presence of esophageal varices (> Grade 2) at risk of bleeding and/or serious or
non-healing wound/ulcer ( as documented by endoscopy)

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 28 days of study entry

- Patients with underlying inflammatory bowel disease, partial or complete bowel
obstruction or chronic diarrhea

- Any of the following within the 12 months prior to study drug administration:
severe/unstable angina, myocardial infarction, coronary artery bypass graft,
symptomatic congestive heart failure, cerebrovascular accident, including transient
ischemic attack, or pulmonary embolism.

- History of cardiac disease:

- active congestive heart failure

- cardiac arrythmias of NCI CTCAE grade >2 or requiring pacemaker

- uncontrolled hypertension

- cardiomyopathy

- atrial fibrillation rate >100bpm

- Patients with factors that increase the risk of QT prolongation or arrhythmic events
( hypokalemia, family history of long QT interval syndrome) or QTc interval of >
450ms for males or > 470ms for females on screening