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

This is a parallel group, randomized, double blind, placebo controlled, multicentre study
designed to assess whether vandetanib (ZD6474) confers an improvement in PFS as compared to
placebo in subject with locally advanced or metastatic papillary or follicular thyroid
carcinoma failing or unsuitable for radioiodine therapy. The trial should be of a sufficient
size so that if vandetanib (ZD6474) is truly active there is a high probability that it will
demonstrate an effect sufficiently promising to warrant a follow-up assessment.

- Subjects will be seen weekly for the first 2 weeks, then again at Week 4, Week 8, and
Week 12 after randomization, and every 12 weeks thereafter. Upon disease progression,
all subjects (both active and placebo) will be unblinded and given the option to
discontinue blinded study treatment and enter follow up and survival, or begin open
label vandetanib (ZD6474) 300 mg treatment. All subjects will be followed to collect
survival data until ≥50% of subjects have died. Subjects who are taking vandetanib
(ZD6474) at the time of study closure and wish to remain on therapy will be allowed to
continue for as long as the Investigator feels that they are obtaining clinical benefit,
or until they are given another anti-cancer therapy. The safety data from all subjects
will be assessed on an ongoing basis, including discontinuation and follow up.

- Radiologic evaluation using RECIST criteria will be performed every 12 weeks (± 2
weeks). All medical images will be centralized assessed at the site and centrally
reviewed. Subjects will be evaluated until progression, and will then be followed up for
survival, regardless of whether they continue randomized treatment, unless they withdraw
consent. Post progression open-label vandetanib (ZD6474) will be offered at the
investigators discretion.

- All subjects must submit a suitable archived tumor sample prior to randomization. In the
event that a suitable archived sample is not available within 2 weeks prior to
randomization, a fresh tumor sample must be obtained in its place prior to
randomization. If a subject undergoes the fresh tumor biopsy procedure, this specimen
will satisfy the first optional tumor biopsy submission should they consent to the
exploratory part of the study.