Study in Asia of the Combination of TACE With Sorafenib in HCC Patients (START)

Inclusion Criteria:

• Age ≧ 18
• life expectancy > 12 weeks

• Histologically diagnosed HCC, OR clinically diagnosed HCC for patients with difficulty in obtaining histological diagnosis. A clinically diagnosed HCC should fulfill ALL the criteria below

  • Chronic hepatitis B or C and/or evidence of liver cirrhosis.
  • Presence of hepatic tumour(s) with image findings compatible with HCC, and no evidence of other gastrointestinal tumours
  • A persistent elevation of serum AFP >= 400 ng/ml without any evidence of an existing α-fetoprotein-secreting germ cell tumour
• Child-Pugh score ≦ 7
• BCLC B
• The patient must have a solitary hepatic tumour greater than 3 cm in diameter or multifocal disease as evidenced by CT or MRI scanning.
• The target lesion must not have been previously treated with local therapy
• The patient must not be a candidate for surgical resection or ablation of the tumour. Size of largest tumor ≦10cm in largest dimension
• Patients who have received previous local therapy treatments (RFA, PEI, cryoablation, surgery, resection) to non-target lesions are eligible
• Local therapy must have been completed at least 4 weeks prior to baseline scan.
• ECOG performance status 0 or 1
• Hb ≧ 9g/dL,
• Absolute neutrophil count > 1000/mm3
• Platelet count ≧ 60x109/L
• Adequate clotting function: INR < 1.5
• Hepatic: AST or ALT < 5 X ULN
• Renal: serum creatinine < 1.5 x ULN
• Bilirubin ≦ 3mg/dL
• The patient must give written, informed consent

Exclusion Criteria:

• Tumor factors

  • Presence of extrahepatic metastasis
  • Predominantly infiltrative lesion
  • Diffuse tumor morphology with extensive lesions involving both lobes.

• Vascular complications

  • Hepatic artery thrombosis, or
  • Partial or complete thrombosis of the main portal vein, or
  • Tumor invasion of portal branch of contralateral lobe, or
  • Hepatic vein tumor thrombus, or
  • Significant arterioportal shunt not amenable to shunt blockage

• Liver function

  • Advanced liver disease: ascites, hepatic encephalopathy
  • Patients with clinically significant gastrointestinal bleeding within the 30 days prior to study entry.

• Others

  • Pregnant or lactating women.
  • Active sepsis or bleeding.
  • Hypersensitivity to intravenous contrast agents.
  • The patient has received prior treatment for HCC target lesion.

  • History of cardiac disease

    • Congestive heart failure > NYHA class 2; active coronary artery disease
    • Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin.
  • Hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management.
  • Therapeutic anticoagulation with coumarin, heparins, or heparinoids.
  • Serious non-healing wounds (including wounds healing by secondary intention), acute or non-healing ulcers, or bone fractures within 3 months.
  • Impairment of swallowing that would preclude administration of sorafenib.
  • The patient is, in the opinion of the investigator, unable and / or unwilling to comply with treatment and study instructions.
  • Previous or concurrent cancer that is distinct in primary site or histology from HCC, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated > 3 years prior to entry is permitted
  • Any active clinically serious infections (> grade 2 NCI-CTCAE ver 3.0)
  • HIV infection or AIDS-related illness or serious acute or chronic illness (based on medical history)