A Randomized, Double Blind, Placebo-controlled Phase II, Multi-Centre Study to Assess the Efficacy and Safety of Vandetanib (ZD6474) in Patients With Locally Advanced or Metastatic Papillary or Follicular Thyroid Carcinoma Failing or Unsuitable for Radioiodine Therapy
- Previously confirmed histological diagnosis of locally advanced or metastatic
papillary or follicular thyroid carcinoma, without anaplastic component. Tumor sample
available for centralized exploratory analysis.
- Presence of one or more measurable lesions at least 1 cm in the longest diameter by
spiral CT scan or 2 cm with conventional techniques.
- Progressive disease following RAI131 or patient unsuitable for RAI131 after surgery.
- Serum TSH<0.5mU/L.
- Major surgery within 4 weeks before randomization.
- Prior chemotherapy within the last 4 weeks prior to randomization.
- RAI131 therapy within 3 months in patients with radioiodine uptake.
- Radiation therapy within the last 4 weeks prior to randomization (with the exception
of palliative radiotherapy).
- Serum bilirubin >1.5 x the upper limit of reference range (ULRR).
- Creatinine clearance < 30 ml/min (calculated by Cockcroft-Gault formula).
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline
phosphatase (ALP) greater than 2.5 × ULRR, or greater than 5.0 × ULRR if judged by
the investigator to be related to liver metastases.
- Clinically significant cardiovascular event (eg myocardial infarction), superior vena
cava [SVC] syndrome, New York Heart Association [NYHA] classification of heart
failure >II within 3 months before entry, or presence of cardiac disease that in the
opinion of the Investigator increases the risk of ventricular arrhythmia.
- History of arrhythmia (multifocal premature ventricular contractions [PVCs],
bigeminy, trigeminy, ventricular tachycardia or uncontrolled atrial fibrillation),
which is symptomatic or requires treatment (CTCAE grade 3), , or asymptomatic
sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by
medication are permitted.
- Congenital long QT syndrome or 1st degree relative with unexplained sudden death
under 40 years of age.