Efficacy and Safety of Vandetanib (ZD6474) in Patients With Metastatic Papillary or Follicular Thyroid Cancer
Condition: Thyroid Neoplasms
MeSH terms: Thyroid Neoplasms; Thyroid Diseases
Intervention: Vandetanib; Placebo
Intervention description: 300 mg oral once daily oral dose
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 165.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: follicular; papillary

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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.