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

November 29, 2023 updated by: Genzyme, a Sanofi Company

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 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

164

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium
        • Research Site
  • Denmark
      • Odense, Denmark
        • Research Site
  • France
      • Angers Cedex, France
        • Research Site
      • Angers Cedex 9, France
        • Research Site
      • Bordeaux Cedex, France
        • Research Site
      • Caen Cedex, France
        • Research Site
      • Caen Cedex 5, France
        • Research Site
      • Lyon, France
        • Research Site
      • Lyon Cedex, France
        • Research Site
      • Marseille Cedex, France
        • Research Site
      • Marseille Cedex 9, France
        • Research Site
      • Paris, France
        • Research Site
      • Paris Cedex 10, France
        • Research Site
      • Paris Cedex 13, France
        • Research Site
      • Villejuif, France
        • Research Site
      • Villejuif Cedex, France
        • Research Site
  • Norway
      • Oslo, Norway
        • Research Site
  • Spain
      • L'Hospitalet de Llobregat, Spain
        • Research Site
      • Madrid, Spain
        • Research Site
  • Sweden
      • Lund, Sweden
        • Research Site
      • Stockholm, Sweden
        • Research Site
  • Switzerland
      • Bern, Switzerland
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 <0.5 mU/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*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. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Other: Placebo
Experimental: vandetanib (ZD6474)
vandetanib (ZD6474) 300 mg per os once daily
Drug: Vandetanib
300 mg oral once daily oral dose
Other Names:
  • SAR390530

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Tumor Progression
Time Frame: Time from date of randomization 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.
Time from date of randomization to date of the first documented tumor progression or date of death from any cause (within the 3 months) of tumor assessment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
46.7 months
Disease Control Rate at 6 Months
Time Frame: 6 months after randomization
number of participants that achieved disease control 6 months after randomization. Best objective response of complete response + partial response + stable disease > 24 weeks according to RECIST criteria
6 months after randomization
Time to Death
Time Frame: time from randomization to date of death
Interim analysis time to date of randomization to date of death (data not mature at the time of this analysis, so number of deaths displayed instead.
time from randomization to date of death

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genzyme, a Sanofi Company

Investigators

  • Study Chair: Clinical Sciences & Operations, Sanofi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 28, 2007

Primary Completion (Actual)

December 2, 2009

Study Completion (Actual)

November 24, 2021

Study Registration Dates

First Submitted

September 27, 2007

First Submitted That Met QC Criteria

September 27, 2007

First Posted (Estimated)

September 28, 2007

Study Record Updates

Last Update Posted (Estimated)

April 19, 2024

Last Update Submitted That Met QC Criteria

November 29, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D4200C00079
  • 2007-001890-27 (EudraCT Number)
  • LPS14940 (Other Identifier: Sanofi)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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