Evaluation of Efficacy, Safety of Vandetanib in Patients With Differentiated Thyroid Cancer

Participants who were receiving vandetanib as randomized treatment will be allowed, upon
re-consent, to continue on open-label vandetanib if in the opinion of the Investigator the
participant is still receiving benefit. Placebo participants who experience disease
progression within 60 days of unblinding may be offered the option of treatment with
open-label vandetanib if, in the Investigator's opinion, such treatment may be of clinical
benefit to the participant. Approximately 2 years; duration will vary depending on individual
participant response.

Inclusion Criteria:

- Provision of informed consent to participate in the study as well as provision of
informed consent to provide a sample of a previously obtained archival tumour biopsy.

- Female or male aged 18 years and older with previously confirmed histological
diagnosis of locally advanced or metastatic differentiated (excluding minimally
invasive follicular) thyroid cancer not amenable to surgical resection, external beam
radiotherapy or local therapy.

- Measurable disease defined as at least one lesion, not irradiated within 12 weeks of
the date of randomisation, that can be accurately measured at baseline.

- Participants must have experienced progression within 14 months and be
RAI-refractory/resistant or unsuitable for RAI.

- Thyroid-stimulating hormone (TSH) suppression below 0.5 mU/L is required.

- World Health Organisation (WHO) or Eastern Cooperative Oncology Group (ECOG)
Performance status 0-2.

- Negative pregnancy test (urine or serum) for female participants of childbearing
potential.

Exclusion Criteria:

- Inadequate organ function as defined by: (1) Alanine aminotransferase (ALT), aspartate
aminotransferase (AST), or alkaline phosphatase (ALP) greater than 2.5 x upper limit
of normal (ULN), or greater than 5.0 x ULN if judged by the Investigator to be related
to liver metastases. (2) Serum bilirubin greater than 1.5 x ULN. This criterion does
not apply to participants with known Gilbert's Disease. (3) Creatinine clearance <50
mL/min (calculated by Cockcroft-Gault formula).

- Risk of prolonged interval between Q and T (QT) on an electrocardiogram (ECG)
corrected for heart rate (QTc) as defined by: (1) Current therapy with any medication
known to be associated with Torsades de pointes or potent inducers of cytochrome
CYP3A4. (2) History of QT prolongation. (3) Congenital long QT syndrome. (4) QT
interval corrected for heart rate by the Bazett's method (QTcB) correction
unmeasurable or greater than 480 ms on screening ECG.

- Previous therapy with approved or investigational tyrosine kinase or anti- vascular
endothelial growth factor (VEGF) receptor inhibitors or targeted therapies (e.g.
multi-targeted kinase inhibitors such as sorafenib, AMG-706, sunitinib, pazopanib,
lenvatinib).

- RAI therapy within 12 weeks prior to first dose of study drug, and radiation therapy
other than RAI, including external beam, if not completed prior to randomization.