Thyroid NeoplasmsPhase 2NCT00537095
Efficacy and Safety of Vandetanib (ZD6474) in Patients With Metastatic Papillary or Follicular Thyroid Cancer
A Phase 2 study testing Vandetanib in people with Thyroid Neoplasms, run by Genzyme, a Sanofi Company at 15 sites in 7 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thyroid Neoplasms
- What is being tested?
- Vandetanib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 164 participants
- Where
- 15 sitesin 7 countries
- Study dates
- 28 Sep 2007to 24 Nov 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Show all 10Show fewer
- 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.
Trial locations and contacts
15 sites in 7 countries.
15 sites in 7 countries
France7 sites
Research Site
Angers
Research Site
Bordeaux
Research Site
Caen
Research Site
Lyon
Research Site
Marseille
Research Site
Paris
Research Site
Villejuif
About this study
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
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
- Being tested
- Vandetanib, Placebo
- Keywords
- follicular, papillary
- Medical subject headings
- Thyroid Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VandetanibDrug
Also called SAR390530
300 mg oral once daily oral dose
PlaceboOther
| Study group | Role | What they receive |
|---|---|---|
| vandetanib (ZD6474) | Experimental | vandetanib (ZD6474) 300 mg per os once daily Receives: Drug: Vandetanib |
| Placebo | Placebo comparator | Placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Tumor Progression
modified RECIST V1.0 was used.
Measured: 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
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
Measured: 6 months after randomization
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
Measured: 46.7 months
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.
Measured: time from randomization to date of death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2007 (estimated)
- Study start28 Sep 2007
- Primary completion2 Dec 2009
- Study completion24 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Thyroid NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 164 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genzyme, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study chair, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00537095
- Sponsor's protocol ID
- D4200C00079
- Other IDs
- 2007-001890-27, LPS14940
- Status last verified
- Nov 2023
- First submitted
- 27 Sep 2007
- Last updated
- 19 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: 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
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.
PubMed 22898678
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00537095
- Acronym / sponsor ID
- D4200C00079
- Conditions
- Thyroid Neoplasms
- Keywords
- follicular, papillary
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 164 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- 28 Sep 2007 (actual)
- Primary completion
- 2 Dec 2009 (actual)
- Study completion
- 24 Nov 2021 (actual)
- First posted
- 28 Sep 2007 (estimated)
- Results
- Posted 8 Jul 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| vandetanib (ZD6474) | Experimental | Drug: Vandetanibvandetanib (ZD6474) 300 mg per os once daily |
| Placebo | Placebo comparator | Other: PlaceboPlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (10 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VandetanibAlso: SAR390530300 mg oral once daily oral dose | Drug | vandetanib (ZD6474) |
| Placebo | Other | Placebo |
Primary outcome
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.
3 secondary outcomes
Disease Control Rate at 6 Months
Time frame: 6 months after randomization
Objective Response Rate
Time frame: 46.7 months
Time to Death
Time frame: time from randomization to date of death
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22898678Leboulleux 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.
- Related InfoLink provided by the sponsor.
- CSR-D4200C00079.pdfLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study chair
Sanofi
15 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vandetanib in people with Thyroid Neoplasms, run by Genzyme, a Sanofi Company at 15 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in France, Spain, Sweden, Belgium, Denmark and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jul 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00537095, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2024.