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

• ClinicalTrials.gov Identifier: NCT00537095
• Recruitment Status: Completed
• First Posted: September 28, 2007
• Results First Posted: July 8, 2011
• Last Update Posted: April 19, 2024
• Sponsor: Genzyme, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Genzyme, a Sanofi Company )

Tracking Information

• First Submitted Date: September 27, 2007
• First Posted Date: September 28, 2007
• Results First Submitted Date: April 27, 2011
• Results First Posted Date: July 8, 2011
• Last Update Posted Date: April 19, 2024
• Actual Study Start Date: September 28, 2007
• Actual Primary Completion Date: December 2, 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 29, 2023)

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.

• Original Primary Outcome Measures (submitted: September 27, 2007): 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

Current Secondary Outcome Measures (submitted: November 29, 2023)

• 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
• 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 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.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of Vandetanib (ZD6474) in Patients With Metastatic Papillary or Follicular Thyroid Cancer
• Official Title: 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

Brief 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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Thyroid Neoplasms

Intervention

• Drug: Vandetanib
  300 mg oral once daily oral dose
  Other Name: SAR390530
• Other: Placebo

Study Arms

• Experimental: vandetanib (ZD6474)
  vandetanib (ZD6474) 300 mg per os once daily
  Intervention: Drug: Vandetanib
• Placebo Comparator: Placebo
  Placebo
  Intervention: Other: Placebo

• Publications *: Leboulleux S, Bastholt L, Krause T, de la Fouchardiere C, Tennvall J, Awada A, Gomez 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 29, 2023): 164
• Original Estimated Enrollment (submitted: September 27, 2007): 135
• Actual Study Completion Date: November 24, 2021
• Actual Primary Completion Date: December 2, 2009 (Final data collection date for primary outcome measure)

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 <0.5 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Denmark, France, Norway, Spain, Sweden, Switzerland
• Removed Location Countries: Portugal

Administrative Information

• NCT Number: NCT00537095
• Other Study ID Numbers: D4200C00079; 2007-001890-27 ( EudraCT Number ); LPS14940 ( Other Identifier: Sanofi )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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

• Current Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
• Original Responsible Party: Not Provided
• Current Study Sponsor: Genzyme, a Sanofi Company
• Original Study Sponsor: AstraZeneca
• Collaborators: Not Provided

Investigators

• Study Chair: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: November 2023