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Phase 2 N=145 Randomized Double-blind Treatment

Efficacy and Safety of Vandetanib (ZD6474) in Patients With Metastatic Papillary or Follicular Thyroid Cancer

Thyroid Neoplasms

Enrolled (actual)
145
Serious AEs
26.3%
Results posted
Jul 2011
Primary outcome: Primary: Time to Tumor Progression — 334; 176 days

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Vandetanib (Drug); Placebo (Other)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Genzyme, a Sanofi Company
Primary completion
Dec 2009

Outcome Measures

OutcomeResultp-value
PRIMARY
Time to Tumor Progression
334; 176
SECONDARY
Disease Control Rate at 6 Months
41; 31
SECONDARY
Objective Response Rate
6; 4
SECONDARY
Time to Death
19; 21

Summary

This was a parallel group, randomized, double blind, placebo controlled, multicentre study designed to assess whether vandetanib (ZD6474) conferred an improvement in PFS as compared to placebo in participants with locally advanced or metastatic papillary or follicular thyroid carcinoma failing or unsuitable for radioiodine therapy. The trial was of a sufficient size so that if vandetanib (ZD6474) was truly active there was a high probability that it would demonstrate an effect sufficiently promising to warrant a follow-up assessment. * Participants were 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 participants (both active and placebo) were 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 participants were followed to collect survival data until greater than or equal to (>=) 50% of participants had died. Participants who were taking vandetanib (ZD6474) at the time of study closure and wished to remain on therapy were allowed to continue for as long as the Investigator felt that they were obtaining clinical benefit, or until they were given another anti-cancer therapy. The safety data from all participants was assessed on an ongoing basis, including discontinuation and follow up. * Radiologic evaluation using RECIST criteria was performed every 12 weeks (+/- 2 weeks). All medical images were centralized assessed at the site and centrally reviewed. Participants were evaluated until progression, and then followed up for survival, regardless of whether they continued randomized treatment, unless they withdrew consent. Post progression open-label vandetanib (ZD6474) were offered at the investigators discretion. * All participants submitted a suitable archived tumor sample prior to randomization. In the event that a suitable archived sample was not available within 2 weeks prior to randomization, a fresh tumor sample was obtained in its place prior to randomization. If a participant underwent the fresh tumor biopsy procedure, this specimen would satisfy the first optional tumor biopsy submission should they consented 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 1.5*the upper limit of reference range (ULRR).
  • Creatinine clearance 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. Participants 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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00537095). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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