CarcinomaPhase 3VITALNCT00532155
A Study of Aflibercept Versus Placebo in Patients With Second-Line Docetaxel for Locally Advanced or Metastatic Non-Small-Cell Lung Cancer
A Phase 3 study testing Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®), Docetaxel (Taxotere®) and Dexamethasone (pre- and post-medication for docetaxel) in people with Carcinoma and Non Small Cell Lung, run by Sanofi at 32 sites in 32 countries.
Trial summary
The primary objective of the study was to demonstrate overall survival improvement for aflibercept + docetaxel compared to docetaxel + placebo as second line treatment for participants with locally advanced or metastatic non-small cell lung cancer (NSCLC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non Small Cell Lung
- What is being tested?
- Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®), Docetaxel (Taxotere®) and Dexamethasone (pre- and post-medication for docetaxel)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 913 participants
- Where
- 32 sitesin 32 countries
- Study dates
- Sep 2007to Oct 2011
- 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
- Histological/cytological proven locally advanced or metastatic non-small cell lung cancer
- Disease progression during or after one, and only one, prior anticancer therapy which is platinum-based for advanced or metastatic disease
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
- Adequate renal, liver and bone marrow functions
Who cannot join
- Squamous histology/cytology
- Less than 28 days elapsed from prior treatment with radiotherapy, surgery, or chemotherapy to the time of randomization
- Prior isotope therapy, whole pelvic radiotherapy, or radiotherapy to > 25% of bone marrow
- Prior docetaxel treatment
- Uncontrolled hypertension
- The above information was not intended to contain all considerations relevant to participation in a clinical trial.
Trial locations and contacts
32 sites in 32 countries.
32 sites in 32 countries
United States1 site
Sanofi-Aventis Administrative Office
Bridgewater, New Jersey, 08807
Australia1 site
sanofi-aventis Australia & New Zealand administrative office
Macquarie Park, New South Wales
United Kingdom1 site
Sanofi-Aventis Admnistrative Office
Guildford Surrey
About this study
Official title: A Multinational, Randomized, Double-Blind Study Comparing Aflibercept Versus Placebo in Patients Treated With Second-Line Docetaxel After Failure of One Platinum Based Therapy for Locally Advanced or Metastatic Non-Small-Cell Lung Cancer
The primary objective of the study was to demonstrate overall survival improvement for aflibercept + docetaxel compared to docetaxel + placebo as second line treatment for participants with locally advanced or metastatic non-small cell lung cancer (NSCLC).
The secondary objectives were to compare other efficacy parameters, to assess the overall safety of the two treatment arms, to assess the pharmacokinetics of intravenous (IV) aflibercept in this participant population and to determine immunogenicity of IV aflibercept in all participants.
Read the detailed description
The study included:
- A screening visit of up to 21 days prior to randomization
- Randomization at baseline (Treatment was initiated with 3 days of randomization)
- A treatment period with 3-week treatment cycles until the participant met the following discontinuation criteria: had progressive disease, had unacceptable toxicity, or refused further study treatment
- A post study treatment follow-up period (a visit was scheduled every 8 weeks until death or end of study)
- Conditions
- Carcinoma, Non Small Cell Lung
- Being tested
- Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®), Placebo, Docetaxel (Taxotere®), Dexamethasone (pre- and post-medication for docetaxel)
- Keywords
- lung cancer, angiogenesis inhibitor, chemotherapy
- Medical subject headings
- Carcinoma, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)Drug
6 mg/kg Aflibercept administered intravenously (IV) over 1 hour once on Day 1, every 3 weeks.
PlaceboDrug
Matching placebo to Aflibercept administered intravenously (IV) over 1 hour once on Day 1, every 3 weeks.
Docetaxel (Taxotere®)Drug
75 mg/m² docetaxel in 250 mL dextrose 5% or NaCl 0.9% administered intravenously (IV) over 1 hour, on Day 1 every 3 weeks.
Dexamethasone (pre- and post-medication for docetaxel)Drug
As a pre- and post-medication for docetaxel, 8 mg dexamethasone was administered orally, the evening before Day 1, on Day 1 (early morning, 1 hour before docetaxel treatment, and evening) and on Day 2 (morning and evening).
| Study group | Role | What they receive |
|---|---|---|
| Aflibercept/Docetaxel | Experimental | Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal. Receives: Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®); Drug: Docetaxel (Taxotere®); Drug: Dexamethasone (pre- and post-medication for docetaxel) |
| Placebo/Docetaxel | Placebo comparator | Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal. Receives: Drug: Placebo; Drug: Docetaxel (Taxotere®); Drug: Dexamethasone (pre- and post-medication for docetaxel) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
OS was time interval from the date of randomization to the date of death due to any cause. If death was not observed during the study, overall survival time was censored at the last date the participant was known to be alive, or the study cutoff date, whichever was earlier. The cut-off date for the OS was date when 687 deaths were observed.
OS was estimated from Kaplan-Meier Curves.
Measured: Baseline to the date when 687 deaths occurred (26 January 2011)
Secondary outcomes (4)
Progression Free Survival (PFS)
PFS was defined as the time interval between the date of randomization and the time of occurrence of the first radiological tumor progression detected by a computer tomography (CT) scan and /or by Magnetic Resonance Imaging (MRI); or death due to any cause; whichever was earlier. Participants without disease progression were censored at the earliest date between their last valid tumour assessment and the data cutoff date.
PFS was estimated from Kaplan-Meier Curves.
Measured: Baseline to data cut-off (26 January 2011)
Overall Response (OR) Rate as Per Response Evaluation Criteria in Solid Tumours (RECIST) Criteria
Participants with OR were those who had a confirmed complete response [CR] or a confirmed partial response [PR], based on RECIST criteria, in which
- CR refected the disappearance of all tumor lesions (with no new tumors)
- PR reflected a pre-defined decrease in tumor burden - a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD
- OR was CR + PR The response rate was the percent of participants with a response.
To determine a response, tumors were assessed by the investigators using Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans; and an observed response was confirmed by repeated imaging after 4 - 6 weeks.
Measured: Baseline to data cut-off (26 January 2011)
Health Related Quality of Life (HRQL) Assessed by the Lung Cancer Symptom Scale (LCSS)
HRQL assessments were performed by participants using a self-administered LCSS questionnaire. LCSS is a 9-item questionnaire, six measuring major symptoms for lung malignancies (appetite, fatigue, cough, dyspnea, hemoptysis and pain), and 3 summation items related to total symptomatic distress, activity status and overall quality of life. Participant responses were measured using visual analogue scales (VAS) with 100-mm lines. The LCSS total score was defined as the mean of the 9 items of the scale, each scored between 0 (for best outcome) to 100 (for worst outcome).
Measured: Baseline (prior to first dose), at cycles 2 and 4 and at the end of study therapy.
Health Related Quality of Life (HRQL) Assessed by the Average Symptom Burden Index (ASBI)
HRQL assessments were performed by participants using a self-administered LCSS questionnaire. LCSS is a 9-item questionnaire, six measuring major symptoms for lung malignancies, and 3 summation items related to total symptomatic distress, activity status and overall quality of life. Participant responses were measured using visual analogue scales (VAS) with 100-mm lines. ABSI was the mean score for the six major lung cancer symptoms (appetite, fatigue, cough, dyspnea, hemoptysis and pain), each scored between 0 (for best outcome) to 100 (for worst outcome).
Measured: Baseline (prior to first dose), at cycles 2 and 4 and at the end of study therapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2007 (estimated)
- Study startSep 2007
- Primary completionJan 2011
- Study completionOct 2011
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 CarcinomaStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 913 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00532155
- Sponsor's protocol ID
- EFC10261
- Other IDs
- EudraCT 2007-000819-29
- Acronym
- VITAL
- Status last verified
- Sep 2025
- First submitted
- 19 Sep 2007
- Last updated
- 10 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Ramlau R, Gorbunova V, Ciuleanu TE, Novello S, Ozguroglu M, Goksel T, Baldotto C, Bennouna J, Shepherd FA, Le-Guennec S, Rey A, Miller V, Thatcher N, Scagliotti G. Aflibercept and Docetaxel versus Docetaxel alone after platinum failure in patients with advanced or metastatic non-small-cell lung cancer: a randomized, controlled phase III trial. J Clin Oncol. 2012 Oct 10;30(29):3640-7. doi: 10.1200/JCO.2012.42.6932. Epub 2012 Sep 10.
PubMed 22965962
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multinational, Randomized, Double-Blind Study Comparing Aflibercept Versus Placebo in Patients Treated With Second-Line Docetaxel After Failure of One Platinum Based Therapy for Locally Advanced or Metastatic Non-Small-Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT00532155
- Acronym / sponsor ID
- VITAL / EFC10261
- Conditions
- Carcinoma, Non Small Cell Lung
- Keywords
- lung cancer, angiogenesis inhibitor, chemotherapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 913 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Study start
- Sep 2007
- Primary completion
- Jan 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 20 Sep 2007 (estimated)
- Results
- Posted 1 Jan 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of the study was to demonstrate overall survival improvement for aflibercept + docetaxel compared to docetaxel + placebo as second line treatment for participants with locally advanced or metastatic non-small cell lung cancer (NSCLC).
The secondary objectives were to compare other efficacy parameters, to assess the overall safety of the two treatment arms, to assess the pharmacokinetics of intravenous (IV) aflibercept in this participant population and to determine immunogenicity of IV aflibercept in all participants.
Detailed description
The study included:
- A screening visit of up to 21 days prior to randomization
- Randomization at baseline (Treatment was initiated with 3 days of randomization)
- A treatment period with 3-week treatment cycles until the participant met the following discontinuation criteria: had progressive disease, had unacceptable toxicity, or refused further study treatment
- A post study treatment follow-up period (a visit was scheduled every 8 weeks until death or end of study)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aflibercept/Docetaxel | Experimental | Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®), Drug: Docetaxel (Taxotere®), Drug: Dexamethasone (pre- and post-medication for docetaxel)Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal. |
| Placebo/Docetaxel | Placebo comparator | Drug: Placebo, Drug: Docetaxel (Taxotere®), Drug: Dexamethasone (pre- and post-medication for docetaxel)Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Histological/cytological proven locally advanced or metastatic non-small cell lung cancer
- Disease progression during or after one, and only one, prior anticancer therapy which is platinum-based for advanced or metastatic disease
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
- Adequate renal, liver and bone marrow functions
Key exclusion criteria (6 listed)
- Squamous histology/cytology
- Less than 28 days elapsed from prior treatment with radiotherapy, surgery, or chemotherapy to the time of randomization
- Prior isotope therapy, whole pelvic radiotherapy, or radiotherapy to > 25% of bone marrow
- Prior docetaxel treatment
- Uncontrolled hypertension
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 |
|---|---|---|
| Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)6 mg/kg Aflibercept administered intravenously (IV) over 1 hour once on Day 1, every 3 weeks. | Drug | Aflibercept/Docetaxel |
| PlaceboMatching placebo to Aflibercept administered intravenously (IV) over 1 hour once on Day 1, every 3 weeks. | Drug | Placebo/Docetaxel |
| Docetaxel (Taxotere®)75 mg/m² docetaxel in 250 mL dextrose 5% or NaCl 0.9% administered intravenously (IV) over 1 hour, on Day 1 every 3 weeks. | Drug | Aflibercept/Docetaxel, Placebo/Docetaxel |
| Dexamethasone (pre- and post-medication for docetaxel)As a pre- and post-medication for docetaxel, 8 mg dexamethasone was administered orally, the evening before Day 1, on Day 1 (early morning, 1 hour before docetaxel treatment, and evening) and on Day 2 (morning and evening). | Drug | Aflibercept/Docetaxel, Placebo/Docetaxel |
Primary outcome
Overall Survival (OS)
Time frame: Baseline to the date when 687 deaths occurred (26 January 2011)
OS was time interval from the date of randomization to the date of death due to any cause. If death was not observed during the study, overall survival time was censored at the last date the participant was known to be alive, or the study cutoff date, whichever was earlier. The cut-off date for the OS was date when 687 deaths were observed. OS was estimated from Kaplan-Meier Curves.
4 secondary outcomes
Progression Free Survival (PFS)
Time frame: Baseline to data cut-off (26 January 2011)
Overall Response (OR) Rate as Per Response Evaluation Criteria in Solid Tumours (RECIST) Criteria
Time frame: Baseline to data cut-off (26 January 2011)
Health Related Quality of Life (HRQL) Assessed by the Lung Cancer Symptom Scale (LCSS)
Time frame: Baseline (prior to first dose), at cycles 2 and 4 and at the end of study therapy.
Health Related Quality of Life (HRQL) Assessed by the Average Symptom Burden Index (ASBI)
Time frame: Baseline (prior to first dose), at cycles 2 and 4 and at the end of study therapy.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22965962Ramlau R, Gorbunova V, Ciuleanu TE, Novello S, Ozguroglu M, Goksel T, Baldotto C, Bennouna J, Shepherd FA, Le-Guennec S, Rey A, Miller V, Thatcher N, Scagliotti G. Aflibercept and Docetaxel versus Docetaxel alone after platinum failure in patients with advanced or metastatic non-small-cell lung cancer: a randomized, controlled phase III trial. J Clin Oncol. 2012 Oct 10;30(29):3640-7. doi: 10.1200/JCO.2012.42.6932. Epub 2012 Sep 10.
Related trials for Carcinoma
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
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
32 sites in 32 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®), Docetaxel (Taxotere®) and Dexamethasone (pre- and post-medication for docetaxel) in people with Carcinoma and Non Small Cell Lung, run by Sanofi at 32 sites in 32 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 6 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 10 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in United States, Argentina, Australia, Austria, Brazil and 27 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 1 Jan 2013). 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: Baseline to the date when 687 deaths occurred (26 January 2011)). 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 NCT00532155, 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 10 Sep 2025.