A Randomised, Double-blind, Parallel Group, Multi-centre, Phase II Study to Assess the Efficacy and Safety of Best Support Care (BSC) Plus ZD6474(Vandetanib) 300 mg, BSC Plus ZD6474(Vandetanib) 100 mg, and BSC Plus Placebo in Patients With Inoperable Hepatocellular Carcinoma (HCC)

This is a multi-centre, phase II study to assess the efficacy and safety of ZD6474 in
patients with Child-Pugh class A, inoperable HCC. This study comprises 2 phases, the primary
treatment phase and the secondary treatment phase. The primary treatment phase is a
randomised, double-blind, parallel-group phase II study to assess the efficacy and safety of
ZD6474 300 mg plus best support care (BSC), ZD6474 100 mg plus BSC, and placebo plus BSC. The
secondary treatment phase is an open-label expanded access program of ZD6474. In the primary
treatment phase, patients will be randomised in a 1:1:1 ratio to receive ZD6474 300 mg plus
BSC, ZD6474 100 mg plus BSC, or placebo plus BSC, respectively. Randomisation will be
stratified on the basis of Cancer of the Liver Italian Programme (CLIP) tumour staging (CLIP
score 0-2 versus 3-4). The primary treatment will continue until objective disease
progression, according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria, or
until patients meet any other withdrawal or discontinuation criteria.The primary endpoint is
tumour stabilisation rate, and the secondary endpoints are objective response rate,
progression-free survival, and overall survival. The purpose of the secondary treatment phase
is to expand the access of ZD6474 so that every patient who is enrolled into this study can
have the chance to receive the active medicine.Once an individual patient has progressive
disease in the primary treatment phase, the blind will be broken for this patient. If this
patient is in the ZD6474 100 mg arm or placebo arm, the patient will be offered the secondary
treatment with ZD6474 300 mg per day. If this patient is randomised to the ZD6474 300 mg arm,
the study medication will be discontinued unless the patient wishes to remain the treatment,
and the patient is to be followed up for survival.