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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
67
Research Site
Tainan, Taiwan
Research Site
Taipei, Taiwan
Research Site
Taoyuan, Taiwan
Tumour Stabilisation Rate
Tumour stabilisation rate calculated as percentage of patients with best objective tumour response (Complete Response, Partial Response or Stable Disease) for \>=16 weeks based on Response Evaluation Criteria in Solid Tumours (RECIST). Complete Response - Disappearance of all target lesions; Partial Response - \>=30% decrease in the sum of longest diameter of target lesions; Progressive Disease - \>=20% increase in the sum of longest diameter of target lesions; Stable Disease - neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time frame: After 16 weeks of treatment.
Objective Response Rate
Objective Response rate defined as percentage of patients with Complete Response \[CR\] or Partial Response \[PR\] based on Response Evaluation Criteria in Solid Tumours (RECIST). Partial response (PR) must have ≥ 30% decrease in the sum of longest diameter of all target lesions as assessed by Magnetic Resonance Imaging (MRI). Complete response (CR) must have disappearance of all target and non-target lesions as assessed by MRI.
Time frame: After 16 weeks of treatment.
Progression-free Survival
Progression-free survival defined as the period from date of randomization(start of treatment) to date of disease progression or death.
Time frame: from the date of randomisation to the date of documented disease progression or death for any cause
Overall Survival
Overall survival defined as the time from randomization (start of treatment) until death from any cause.
Time frame: assessed up to 360 days
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