A Study of Aflibercept Versus Placebo in Patients With Second-Line Docetaxel for Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (VITAL)

September 8, 2025 updated by: Sanofi

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

913

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina
        • Sanofi-Aventis Administrative Office
  • Australia
    • New South Wales
      • Macquarie Park, New South Wales, Australia
        • sanofi-aventis Australia & New Zealand administrative office
  • Austria
      • Vienna, Austria
        • Sanofi-Aventis Administrative Office
  • Brazil
      • São Paulo, Brazil
        • Sanofi-Aventis Administrative Office
  • Bulgaria
      • Sofia, Bulgaria
        • Sanofi-Aventis Administrative Office
  • Canada
      • Laval, Canada
        • Sanofi-Aventis Administrative Office
  • Chile
      • Santiago, Chile
        • Sanofi-Aventis Administrative Office
  • China
      • Shanghai, China
        • Sanofi-Aventis Administrative Office
  • Czechia
      • Prague, Czechia
        • Sanofi-Aventis Administrative Office
  • Estonia
      • Tallinn, Estonia
        • Sanofi-Aventis Administrative Office
  • Finland
      • Helsinki, Finland
        • Sanofi-Aventis Administrative Office
  • France
      • Paris, France
        • Sanofi-Aventis Administrative Office
  • Germany
      • Berlin, Germany
        • Sanofi-Aventis Administrative Office
  • Greece
      • Athens, Greece
        • Sanofi-Aventis Administrative Office
  • Hong Kong
      • Causeway Bay, Hong Kong
        • Sanofi-Aventis Administrative Office
  • Hungary
      • Budapest, Hungary
        • Sanofi-Aventis Administrative Office
  • India
      • Mumbai, India
        • Sanofi-Aventis Administrative Office
  • Italy
      • Milan, Italy
        • Sanofi-Aventis Administrative Office
  • Malaysia
      • Kuala Lumpur, Malaysia
        • Sanofi-Aventis Administrative Office
  • Netherlands
      • Gouda, Netherlands
        • Sanofi-Aventis Administrative Office
  • Poland
      • Warsaw, Poland
        • Sanofi-Aventis Administrative Office
  • Portugal
      • Porto Salvo, Portugal
        • Sanofi-Aventis Administrative Office
  • Romania
      • Bucharest, Romania
        • Sanofi-Aventis Administrative Office
  • Russia
      • Moscow, Russia
        • Sanofi-Aventis Administrative Office
  • Singapore
      • Singapore, Singapore
        • Sanofi-Aventis Administrative Office
  • South Korea
      • Seoul, South Korea
        • Sanofi-Aventis Administrative Office
  • Spain
      • Barcelona, Spain
        • Sanofi-Aventis Administrative Office
  • Sweden
      • Bromma, Sweden
        • Sanofi-Aventis Administrative Office
  • Taiwan
      • Taipei, Taiwan
        • Sanofi-Aventis Administrative Office
  • Turkey (Türkiye)
      • Istanbul, Turkey (Türkiye)
        • Sanofi-Aventis Administraive Office
  • United Kingdom
      • Guildford Surrey, United Kingdom
        • Sanofi-Aventis Admnistrative Office
  • United States
    • New Jersey
      • Bridgewater, New Jersey, United States, 08807
        • Sanofi-Aventis Administrative Office

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Aflibercept/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.
Drug: 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: 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 (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
6 mg/kg Aflibercept administered intravenously (IV) over 1 hour once on Day 1, every 3 weeks.
Placebo Comparator: Placebo/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.
Drug: Placebo
Matching placebo to Aflibercept administered intravenously (IV) over 1 hour once on Day 1, every 3 weeks.
Drug: 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: 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline to the date when 687 deaths occurred (26 January 2011)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: Baseline to data cut-off (26 January 2011)

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.
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)

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.
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.
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).
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.
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).
Baseline (prior to first dose), at cycles 2 and 4 and at the end of study therapy.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sanofi

Collaborators

Regeneron Pharmaceuticals

Investigators

  • Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2007

Primary Completion (Actual)

January 1, 2011

Study Completion (Actual)

October 1, 2011

Study Registration Dates

First Submitted

September 19, 2007

First Submitted That Met QC Criteria

September 19, 2007

First Posted (Estimated)

September 20, 2007

Study Record Updates

Last Update Posted (Estimated)

September 10, 2025

Last Update Submitted That Met QC Criteria

September 8, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EFC10261
  • EudraCT 2007-000819-29

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Carcinoma

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Dominican Republic

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe