Phase II Study of Best Support Care (BSC) Plus ZD6474(Vandetanib) in Patients With Inoperable Hepatocellular Carcinoma (HCC)

Inclusion Criteria

• Able to understand and provide informed consent
• Histologically diagnosed HCC, OR clinically diagnosed HCC for patients with difficulty in obtaining histological diagnosis. A clinically diagnosed HCC should fulfil ALL the criteria below.
• Chronic hepatitis B or C and/or evidence of liver cirrhosis
• Presence of hepatic tumour(s) with image findings (sonography, CT scan, or MRI scan) compatible with HCC, and no evidence of other gastrointestinal tumours
• A persistent elevation of serum a-fetoprotein level >= 400 ng/ml without any evidence of an existing a-fetoprotein-secreting germ cell tumour
• Locally advanced (for example, portal vein invasion, multiple nodules, or nodules in both lobes) or metastatic HCC with at least one measurable lesion by RECIST criteria that meets ANY the criteria below:
• HCC not suitable to receive local therapy, including surgical resection, percutaneous ethanol injection (PEI), or transarterial chemo-embolization (TACE)
• Disease recurred or was refractory to previous local therapy
• Patients refused local therapy
• At least one measurable lesion by RECIST criteria. Tumour lesions treated previously with local radiotherapy, percutaneous ethanol injection, radiofrequency ablation, or transarterial embolization are NOT considered measurable.
• If they completed percutaneous ethanol injection, radiofrequency ablation, transarterial embolization, or cryotherapy at least 4 weeks prior to enrollment, patients must have subsequent progression or recurrence with at least one new measurable lesion that has not been treated with any local procedure.
• Karnofsky performance status >= 70
• Life expectancy >= 2 months
• Child-Pugh class A liver function
• Adequate bone marrow reserve, defined as white blood cell count >= 3,000/ml, and platelet count >= 75,000/ml
• Liver transaminases (AST and ALT) 120 mg/m2, mitomycin-C > 24 mg/m2, cisplatin > 120 mg/m2, or 5-fluorouracil > 2400 mg/m2
• Details of the TACE or HAI regimens are not available in the chart
• (Note: The number of sessions of prior TACE or HAI will not be limited for patients who have no target lesion in the liver).
• Local treatment including radiotherapy (except palliative radiotherapy), percutaneous ethanol injection, radiofrequency ablation, transarterial embolization, or cryotherapy completed within 4 weeks prior to enrollment
• Prior therapy targeting VEGF or EGF signalling pathways, including but not limited to bevacizumab, cetuximab, gefitinib, erlotinib, or sorafenib.
• Prior thalidomide therapy is not allowed but for patients who stop thalidomide due to intolerability and meet either one of following condition can be included:
• Patients who took thalidomide for no more than 3 days but 2 within 3 months before entry; or other cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia.
• History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation), which is symptomatic, requires treatment (CTCAE grade 3), or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, if controlled on medication, will not be excluded.
• Previous history of QTc prolongation as a result of therapy with other medication that required discontinuation of that medication.
• Congenital long QT syndrome, or first-degree relative with unexplained sudden death under 40 years of age
• Presence of left bundle branch block
• QTc with Bazett's correction that is unmeasurable, or >= 480 msec on screening ECG
• Use of any concomitant medication that are generally accepted by authorities to have a risk of causing Torsades de Pointes within 2 weeks before enrollment (use of the concomitant medication that may be associated with Torsades de Pointes but lack substantial evidence of causing Torsades de Pointes is allowed, but the screening QTc must be less then 460 msec, and an additional ECG is required with