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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00537095
Recruitment Status : Active, not recruiting
First Posted : September 28, 2007
Results First Posted : July 8, 2011
Last Update Posted : December 7, 2017
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

September 27, 2007
September 28, 2007
April 27, 2011
July 8, 2011
December 7, 2017
September 29, 2007
December 2009   (Final data collection date for primary outcome measure)
Time to Tumor Progression [ Time Frame: Time from date of randomisation to date of the first documented tumor progression or date of death from any cause (within the 3 months) of tumor assessment ]
modified RECIST V1.0 was used
To demonstrate an improvement in progression free survival (PFS) with ZACTIMA™ (ZD6474) 300 mg as compared to Placebo in subjects with locally advanced or metastatic papillary or follicular Thyroid Carcinoma failing or unsuitable for Radioiodine therapy
Complete list of historical versions of study NCT00537095 on Archive Site
  • Disease Control Rate at 6 Months [ Time Frame: 6 months after randomisation ]
    number of participants that achieved disease control 6 months after randomisation. Best objective response of complete response + partial response + stable disease > 24 weeks according to RECIST criteria
  • Objective Response Rate [ Time Frame: 46.7 months ]
    Best objective response of the participants from an average of 46.7 months, defined as complete or partial response according to RECIST criteria
  • Time to Death [ Time Frame: time from randomisation to date of death ]
    Interim analysis time to date of randomisation to date of death (data not mature at the time of this analysis, so number of deaths displayed instead.
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Efficacy and Safety of Vandetanib (ZD6474) in Patients With Metastatic Papillary or Follicular Thyroid Cancer
A Randomized, Double Blind, Placebo-controlled Phase II, Multi-Centre Study to Assess the Efficacy and Safety of Vandetanib (ZD6474) in Patients With Locally Advanced or Metastatic Papillary or Follicular Thyroid Carcinoma Failing or Unsuitable for Radioiodine Therapy

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.
Not Provided
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Thyroid Neoplasms
  • Drug: Vandetanib
    300 mg oral once daily oral dose
    Other Name: SAR390530
  • Other: Placebo
  • Experimental: vandetanib (ZD6474)
    vandetanib (ZD6474) 300 mg per os once daily
    Intervention: Drug: Vandetanib
  • Placebo Comparator: Placebo
    Intervention: Other: Placebo
Leboulleux S, Bastholt L, Krause T, de la Fouchardiere C, Tennvall J, Awada A, Gómez JM, Bonichon F, Leenhardt L, Soufflet C, Licour M, Schlumberger MJ. Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 2 trial. Lancet Oncol. 2012 Sep;13(9):897-905. doi: 10.1016/S1470-2045(12)70335-2. Epub 2012 Aug 14.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Active, not recruiting
December 31, 2019
December 2009   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
Belgium,   Denmark,   France,   Norway,   Spain,   Sweden,   Switzerland
2007-001890-27 ( EudraCT Number )
LPS14940 ( Other Identifier: Sanofi )
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Not Provided
Sanofi ( Genzyme, a Sanofi Company )
Genzyme, a Sanofi Company
Not Provided
Study Chair: Clinical Sciences & Operations Sanofi
November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP