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

Thyroid Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00537095
• Other study ID #: D4200C00079
• Secondary ID: 2007-001890-27LP
• Status: Completed
• Phase: Phase 2
• Start date: September 28, 2007
• Est. completion date: November 24, 2021

Study information

• Verified date: November 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 164
• Est. completion date: November 24, 2021
• Est. primary completion date: December 2, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Thyroid Diseases
• Thyroid Neoplasms

Intervention

Drug:
• Vandetanib
300 mg oral once daily oral dose

Other:
• Placebo

Locations

Country	Name	City	State
Belgium	Research Site	Brussels
Denmark	Research Site	Odense
France	Research Site	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
Norway	Research Site	Oslo
Spain	Research Site	L'Hospitalet de Llobregat
Spain	Research Site	Madrid
Sweden	Research Site	Lund
Sweden	Research Site	Stockholm
Switzerland	Research Site	Bern

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Countries where clinical trial is conducted

Belgium,  Denmark,  France,  Norway,  Spain,  Sweden,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Disease Control Rate at 6 Months	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
Secondary	Objective Response Rate	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
Secondary	Time to 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

External Links

•   CSR-D4200C00079.pdf
•   Related Info