Clinical trial NCT00537095: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Thyroid Neoplasms
Keywords: follicular
papillary
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2007-09-28
Enrollment: 164
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Time to Tumor Progression
timeFrame: 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:
measure: Disease Control Rate at 6 Months
timeFrame: 6 months after randomization
measure: Objective Response Rate
timeFrame: 46.7 months
measure: Time to Death
timeFrame: time from randomization to date of death
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Research Site
city: Odense
country: Denmark
facility: Research Site
city: Angers Cedex 9
country: France
facility: Research Site
city: Angers Cedex
country: France
facility: Research Site
city: Bordeaux Cedex
country: France
facility: Research Site
city: Caen Cedex 5
country: France
facility: Research Site
city: Caen Cedex
country: France
facility: Research Site
city: Lyon Cedex
country: France
facility: Research Site
city: Lyon
country: France
facility: Research Site
city: Marseille Cedex 9
country: France
facility: Research Site
city: Marseille Cedex
country: France
facility: Research Site
city: Paris Cedex 10
country: France
facility: Research Site
city: Paris Cedex 13
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Villejuif Cedex
country: France
facility: Research Site
city: Villejuif
country: France
facility: Research Site
city: Oslo
country: Norway
facility: Research Site
city: L'Hospitalet de Llobregat
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Bern
country: Switzerland
facility: Research Site
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_CHAIR
References:
citation: 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.