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

 To determine the efficacy (as assessed by progression-free survival [PFS]) of vandetanib when
 compared to placebo in participants with differentiated thyroid cancer that is either locally
 advanced or metastatic who are refractory or unsuitable for radioiodine therapy.

 Secondary Objectives:

 -  To determine the efficacy of vandetanib when compared to placebo in this participant
 population as assessed by efficacy variables including duration of response (DOR),
 objective response rate (ORR), change in tumour size (TS) and overall survival (OS).

 -  To evaluate the pharmacokinetics (PK) of vandetanib in this participant population and
 potentially investigate any influence of participant demography and pathophysiology on
 vandetanib PK.

 -  To demonstrate an improvement in time to worsening of pain (TWP) in participants treated
 with vandetanib when compared to placebo in this participant population.

 -  To evaluate the safety and tolerability of vandetanib treatment in this participant
 population.
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.