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

NCT00537095 | Completed Phase 2 Results

• 3 other identifiers: D4200C000792007-001890-27LPS14940
• Study Type: interventional
• Target: 164
• Locations: 7 countries
• Sites: 15

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.

Conditions

Thyroid Neoplasms

Keywords

follicular; papillary

Outcome Measures

Primary Outcomes (1)

• Time to Tumor Progression

  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 Outcomes (3)

• Disease Control Rate at 6 Months

  6 months after randomization

• Objective Response Rate

  46.7 months

• Time to Death

  time from randomization to date of death

Study Arms (2)

vandetanib (ZD6474)

EXPERIMENTAL

vandetanib (ZD6474) 300 mg per os once daily

Drug: Vandetanib

Placebo

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

Vandetanib DRUG

300 mg oral once daily oral dose

Also known as: SAR390530

vandetanib (ZD6474)

Placebo OTHER

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (15)

Research Site

Brussels, Belgium

Location

Research Site

Odense, Denmark

Location

Research Site

Angers, France

Location

Research Site

Bordeaux, France

Location

Research Site

Caen, France

Location

Research Site

Lyon, France

Location

Research Site

Marseille, France

Location

Research Site

Paris, France

Location

Research Site

Villejuif, France

Location

Research Site

Oslo, Norway

Location

Research Site

L'Hospitalet de Llobregat, Spain

Location

Research Site

Madrid, Spain

Location

Research Site

Lund, Sweden

Location

Research Site

Stockholm, Sweden

Location

Research Site

Bern, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 22898678 DERIVED

Related Links

• Related Info
• CSR-D4200C00079.pdf

MeSH Terms

Conditions

Thyroid Neoplasms

Interventions

vandetanib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2007
• First Posted: September 28, 2007
• Study Start: September 28, 2007
• Primary Completion: December 2, 2009
• Study Completion: November 24, 2021
• Last Updated: April 19, 2024
• Results First Posted: July 8, 2011

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share

Locations

FR (7); DK (1); NO (1); CH (1); ES (2); SE (2); BE (1)