Non-Small-Cell Lung CarcinomaPhase 3NCT00404924
ZD6474 (ZACTIMA™) Phase III Study in EGFR Failures
A Phase 3 study testing ZD6474 (vandetanib) in people with Non-Small-Cell Lung Carcinoma, run by Genzyme, a Sanofi Company at 102 sites in 22 countries.
Trial summary
This study is being carried out to assess if adding ZD6474 to best supportive care (BSC) is more effective than best supportive care alone, for the treatment of patients with non-small cell lung cancer, whose disease has recurred after previous chemotherapy and an Epidermal Growth Factor Receptor Tyrosine Kinase… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small-Cell Lung Carcinoma
- What is being tested?
- ZD6474 (vandetanib)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,140 participants
- Where
- 102 sitesin 22 countries
- Study dates
- Nov 2006to Nov 2014
- Phase
- Phase 3
- 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
- Patients with Non-small cell lung cancer for which the standard cancer treatments of surgery, chemotherapy, radiation or other anticancer drugs are no longer appropriate treatments for you.
Who cannot join
- Patients who have had standard cancer treatments of surgery, chemotherapy or other systemic anti-cancer therapy within 4 weeks before start of study therapy.
- Three or more prior chemotherapy regimens.
- Significant cardiovascular events.
Trial locations and contacts
102 sites in 22 countries.
102 sites in 22 countries
Germany12 sites
Research Site
Bad Berka
Research Site
Donaustauf
Research Site
Frankfurt
Research Site
Gauting
Research Site
Göttingen
Research Site
Halle
Research Site
Hanover
Research Site
Karlsruhe
Research Site
Leipzig
Research Site
Löwenstein
Research Site
Mannheim
Research Site
München
Italy12 sites
Research Site
Ancona
Research Site
Bologna
Research Site
Catania
Research Site
Genova
Research Site
Milan
Research Site
Orbassano
Research Site
Parma
Research Site
Roma
Research Site
Rozzano
Research Site
S.Andrea Delle Fratte
Research Site
Sondalo
Research Site
Udine
China8 sites
Research Site
Beijing
Research Site
Chengdu
Research Site
Dalian
Research Site
Guangzhou
Research Site
Nanjing
Research Site
Shanghai
Research Site
Wuhan
Research Site
Xi'an
Belgium7 sites
Research Site
Antwerp
Research Site
Brussels (Woluwé-St-Lambert)
Research Site
Charleroi
Research Site
Edegem
Research Site
Ghent
Research Site
Leuven
Research Site
Liège
France7 sites
Research Site
Brest
Research Site
Caen
Research Site
Lyon
Research Site
Marseille
Research Site
Nice
Research Site
Pierre-Bénite
Research Site
Toulon Armees
Taiwan7 sites
Research Site
Changhua
Research Site
Kaohsiung City
Research Site
Kaohsiung Hsien
Research Site
Liou Ying Township
Research Site
Taichung
Research Site
Taipei
Research Site
Taoyuan
Argentina6 sites
Research Site
Bahía Blanca
Research Site
Ciudad de Buenos Aires
Research Site
La Plata
Research Site
Rosario
Research Site
San Miguel de Tucumán
Research Site
Santa Fe
Australia5 sites
Research Site
Fitzroy
Research Site
Perth
Research Site
St Leonards
Research Site
Tugan
Research Site
Woodville South
United Kingdom5 sites
Research Site
Birmingham
Research Site
Chelmsford
Research Site
Dundee
Research Site
Maidstone
Research Site
Manchester
Canada4 sites
Research Site
Edmonton, Alberta
Research Site
Montreal, Quebec
Research Site
Oshawa, Ontario
Research Site
Toronto, Ontario
Israel4 sites
Research Site
Jerusalem
Research Site
Kfar Saba
Research Site
Tel HaShomer
Research Site
Tsrifin
South Korea4 sites
Research Site
Goyang-si
Research Site
Seongnam
Research Site
Seoul
Research Site
Suwon
Spain4 sites
Research Site
Baracaldo(Vizcaya)
Research Site
Barcelona
Research Site
Santander
Research Site
Valencia
Philippines3 sites
Research Site
Cebu City
Research Site
Manila
Research Site
Quezon City
Thailand3 sites
Research Site
Bangkok
Research Site
Chiang Mai
Research Site
Khon Kaen
United States2 sites
Research Site
Germantown, Tennessee
Research Site
Tucson, Arizona
About this study
Official title: A Phase III Study to Assess the Efficacy of ZD6474 (ZACTIMA™) Plus Best Supportive Care Versus Best Supportive Care in Patients With Locally Advanced or Metastatic (Stage IIIB-IV) Non-Small Cell Lung Cancer After Therapy With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI)
This study is being carried out to assess if adding ZD6474 to best supportive care (BSC) is more effective than best supportive care alone, for the treatment of patients with non-small cell lung cancer, whose disease has recurred after previous chemotherapy and an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI). ZD6474 is a new anti-cancer drug in development that works in a different way to standard chemotherapy drugs. It targets the growth of new blood vessels to a tumour and thereby might slow the rate at which the tumour may grow. Early studies indicate that ZD6474 has a positive effect on the time that a tumour may take to progress to a further stage. Approximately 930 patients will take part in this study. It will be conducted in hospitals and clinics in North and South America, Europe and Asia.
- Conditions
- Non-Small-Cell Lung Carcinoma
- Being tested
- ZD6474 (vandetanib), Best Supportive Care
- Keywords
- Non-Small-Cell Lung Carcinoma, Adenocarcinoma, Squamous Cell Carcinoma, Large Cell Carcinoma
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Adenocarcinoma, Carcinoma, Squamous Cell, Carcinoma, Large Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZD6474 (vandetanib)Drug
Also called ZACTIMA™
once daily oral tablet
Best Supportive CareOther
standard of care
| Study group | Role | What they receive |
|---|---|---|
| 1 | Placebo comparator | Best Supportive Care Receives: Other: Best Supportive Care |
| 2 | Experimental | Vandetanib + Best Supportive Care Receives: Drug: ZD6474 (vandetanib); Other: Best Supportive Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
Overall Survival (OS) is defined as the time from date of randomization until death. Any blinded/unknown patient which have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive (ie, their status must be known at the censored date and should not be lost to follow up or unknown).
Measured: Time to death in months
Secondary outcomes (5)
Progression-Free Survival (PFS)
Median time (in months) from randomisation until objective disease progression (determined by RECIST assessments) or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment
Measured: RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression
Objective Response Rate (ORR)
The ORR is the number of patients that are responders ie those patients with a confirmed best objective response of complete response (CR) or partial response (PR) as defined by RECIST criteria.
The categories for best objective response are CR, PR, stable disease (SD)>= 8 weeks, progressive disease (PD) or NE.
Measured: Each patient was assessed for objective response from the sequence of RECIST scan data up to data cut off. RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression.
Disease Control Rate (DCR)
Disease control rate is defined as the number of patients who achieved disease control at 8 weeks following randomisation. Disease control at 8 weeks is defined as a best objective response of complete response (CR), partial response (PR) or stable disease (SD) >= 8 weeks
Measured: RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression
Duration of Response (DoR)
Response is defined as a confirmed best objective response of CR or PR. Duration of response is defined as time from the date of first documented response until date of documented progression or death in the absence of disease progression (provided death is within 3 months of last RECIST assessment)
Measured: RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression
Time to Deterioration of Disease-related Symptoms (TDS) by Questionnaire - the Lung Cancer Subscale (LCS) a Selection of the FACT-L Focusing on Symptoms of Lung Cancer Plus Pain and Fatigue (LCS-PF)
Time to deterioration in symptoms is defined as the interval from the date of randomization to the first assessment of 'worsened' with no visit assessment of 'improved' within the next 28 days. Where assessment is by a selection of questions from the Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L) questionnaire.
Measured: Disease-related symptom assessments are to be administered at screening (within 7 days before the first dose of study medication) and every 4 weeks thereafter, at discontinuation of study treatment and at the 30-day follow-up visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2006 (estimated)
- Study startNov 2006
- Primary completionOct 2009
- Study completionNov 2014
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 Non-Small-Cell Lung CarcinomaStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,140 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 director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00404924
- Sponsor's protocol ID
- D4200C00044
- Other IDs
- EUDRACT Number 2006-002384-12
- Status last verified
- Aug 2016
- First submitted
- 28 Nov 2006
- Last updated
- 30 Sep 2016
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Platt A, Morten J, Ji Q, Elvin P, Womack C, Su X, Donald E, Gray N, Read J, Bigley G, Blockley L, Cresswell C, Dale A, Davies A, Zhang T, Fan S, Fu H, Gladwin A, Harrod G, Stevens J, Williams V, Ye Q, Zheng L, de Boer R, Herbst RS, Lee JS, Vasselli J. A retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies. BMC Cancer. 2015 Mar 23;15:171. doi: 10.1186/s12885-015-1146-8.
PubMed 25881079
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Study to Assess the Efficacy of ZD6474 (ZACTIMA™) Plus Best Supportive Care Versus Best Supportive Care in Patients With Locally Advanced or Metastatic (Stage IIIB-IV) Non-Small Cell Lung Cancer After Therapy With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI)
- ClinicalTrials.gov ID
- NCT00404924
- Acronym / sponsor ID
- D4200C00044
- Conditions
- Non-Small-Cell Lung Carcinoma
- Keywords
- Non-Small-Cell Lung Carcinoma, Adenocarcinoma, Squamous Cell Carcinoma, Large Cell Carcinoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,140 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- Nov 2006
- Primary completion
- Oct 2009 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 29 Nov 2006 (estimated)
- Results
- Posted 26 Mar 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being carried out to assess if adding ZD6474 to best supportive care (BSC) is more effective than best supportive care alone, for the treatment of patients with non-small cell lung cancer, whose disease has recurred after previous chemotherapy and an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI). ZD6474 is a new anti-cancer drug in development that works in a different way to standard chemotherapy drugs. It targets the growth of new blood vessels to a tumour and thereby might slow the rate at which the tumour may grow. Early studies indicate that ZD6474 has a positive effect on the time that a tumour may take to progress to a further stage. Approximately 930 patients will take part in this study. It will be conducted in hospitals and clinics in North and South America, Europe and Asia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Placebo comparator | Other: Best Supportive CareBest Supportive Care |
| 2 | Experimental | Drug: ZD6474 (vandetanib), Other: Best Supportive CareVandetanib + Best Supportive Care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients with Non-small cell lung cancer for which the standard cancer treatments of surgery, chemotherapy, radiation or other anticancer drugs are no longer appropriate treatments for you.
Key exclusion criteria (3 listed)
- Patients who have had standard cancer treatments of surgery, chemotherapy or other systemic anti-cancer therapy within 4 weeks before start of study therapy.
- Three or more prior chemotherapy regimens.
- Significant cardiovascular events.
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 |
|---|---|---|
| ZD6474 (vandetanib)Also: ZACTIMA™once daily oral tablet | Drug | 2 |
| Best Supportive Carestandard of care | Other | 1, 2 |
Primary outcome
Overall Survival (OS)
Time frame: Time to death in months
Overall Survival (OS) is defined as the time from date of randomization until death. Any blinded/unknown patient which have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive (ie, their status must be known at the censored date and should not be lost to follow up or unknown).
5 secondary outcomes
Progression-Free Survival (PFS)
Time frame: RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression
Objective Response Rate (ORR)
Time frame: Each patient was assessed for objective response from the sequence of RECIST scan data up to data cut off. RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression.
Disease Control Rate (DCR)
Time frame: RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression
Duration of Response (DoR)
Time frame: RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression
Time to Deterioration of Disease-related Symptoms (TDS) by Questionnaire - the Lung Cancer Subscale (LCS) a Selection of the FACT-L Focusing on Symptoms of Lung Cancer Plus Pain and Fatigue (LCS-PF)
Time frame: Disease-related symptom assessments are to be administered at screening (within 7 days before the first dose of study medication) and every 4 weeks thereafter, at discontinuation of study treatment and at the 30-day follow-up visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25881079Platt A, Morten J, Ji Q, Elvin P, Womack C, Su X, Donald E, Gray N, Read J, Bigley G, Blockley L, Cresswell C, Dale A, Davies A, Zhang T, Fan S, Fu H, Gladwin A, Harrod G, Stevens J, Williams V, Ye Q, Zheng L, de Boer R, Herbst RS, Lee JS, Vasselli J. A retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies. BMC Cancer. 2015 Mar 23;15:171. doi: 10.1186/s12885-015-1146-8.
- Related InfoLink provided by the sponsor.
- CSR-D4200C00044.pdfLink provided by the sponsor.
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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 director
Sanofi
102 sites in 22 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ZD6474 (vandetanib) in people with Non-Small-Cell Lung Carcinoma, run by Genzyme, a Sanofi Company at 102 sites in 22 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 1 inclusion and 3 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 30 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 102 sites in Germany, Italy, China, Belgium, France and 17 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 26 Mar 2012). 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?
Overall Survival (OS) (time frame: Time to death in months). 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 NCT00404924, 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 30 Sep 2016.