Evaluation of Efficacy, Safety of Vandetanib in Patients With Differentiated Thyroid Cancer
Condition: Differentiated Thyroid Cancer
MeSH terms: Thyroid Neoplasms; Thyroid Diseases
Intervention: Vandetanib (SAR390530); Placebo
Intervention description: Pharmaceutical form: tablet
Route of administration: oral; Pharmaceutical form: tablet
Route of administration: oral
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 243.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: vandetanib, AZD 6474, Differentiated Thyroid Cancer

Summary:

      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.
    

Eligibility criteria:

        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.