Efficacy and Safety of Vandetanib (ZD6474) in Patients With Metastatic Papillary or Follicular Thyroid Cancer
This is a parallel group, randomized, double blind, placebo controlled, multicentre study designed to assess whether vandetanib (ZD6474) confers an improvement in PFS as compared to placebo in subject with locally advanced or metastatic papillary or follicular thyroid carcinoma failing or unsuitable for radioiodine therapy. The trial should be of a sufficient size so that if vandetanib (ZD6474) is truly active there is a high probability that it will demonstrate an effect sufficiently promising to warrant a follow-up assessment.
- Subjects will be 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 subjects (both active and placebo) will be 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 subjects will be followed to collect survival data until ≥50% of subjects have died. Subjects who are taking vandetanib (ZD6474) at the time of study closure and wish to remain on therapy will be allowed to continue for as long as the Investigator feels that they are obtaining clinical benefit, or until they are given another anti-cancer therapy. The safety data from all subjects will be assessed on an ongoing basis, including discontinuation and follow up.
- Radiologic evaluation using RECIST criteria will be performed every 12 weeks (± 2 weeks). All medical images will be centralized assessed at the site and centrally reviewed. Subjects will be evaluated until progression, and will then be followed up for survival, regardless of whether they continue randomized treatment, unless they withdraw consent. Post progression open-label vandetanib (ZD6474) will be offered at the investigators discretion.
- All subjects must submit a suitable archived tumor sample prior to randomization. In the event that a suitable archived sample is not available within 2 weeks prior to randomization, a fresh tumor sample must be obtained in its place prior to randomization. If a subject undergoes the fresh tumor biopsy procedure, this specimen will satisfy the first optional tumor biopsy submission should they consent to the exploratory part of the study.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|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|
- Time to Tumor Progression [ Time Frame: Time from date of randomisation to date of the first documented tumor progression or date of death from any cause (within the 3 months) of tumor assessment ] [ Designated as safety issue: No ]modified RECIST V1.0 was used
- Disease Control Rate at 6 Months [ Time Frame: 6 months after randomisation ] [ Designated as safety issue: No ]number of participants that achieved disease control 6 months after randomisation. Best objective response of complete response + partial response + stable disease > 24 weeks according to RECIST criteria
- Objective Response Rate [ Time Frame: 46.7 months ] [ Designated as safety issue: No ]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 randomisation to date of death ] [ Designated as safety issue: No ]Interim analysistime to date of randomisation to date of death (data not mature at the time of this analysis, so number of deaths displayed instead.
|Study Start Date:||September 2007|
|Estimated Study Completion Date:||May 2017|
|Primary Completion Date:||December 2009 (Final data collection date for primary outcome measure)|
Experimental: vandetanib (ZD6474)
vandetanib (ZD6474) 300 mg per os once daily
300 mg oral once daily oral dose
Placebo Comparator: Placebo
Please refer to this study by its ClinicalTrials.gov identifier: NCT00537095
|Angers Cedex 9, France|
|Angers Cedex, France|
|Bordeaux Cedex, France|
|Caen Cedex 5, France|
|Caen Cedex, France|
|Lyon Cedex, France|
|Marseille Cedex 9, France|
|Marseille Cedex, France|
|Paris Cedex 10, France|
|Paris Cedex 13, France|
|Villejuif Cedex, France|
|L'Hospitalet de Llobregat, Spain|
|Study Chair:||Annie Tisseron||AstraZeneca|
|Principal Investigator:||Martin Schlumberger, MD||Institut Gustave Roussy, France|
|Study Director:||Peter Langmuir, MD||AstraZeneca|