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

Primary Purpose

Carcinoma, Non Small Cell Lung

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Placebo
Docetaxel (Taxotere®)
Dexamethasone (pre- and post-medication for docetaxel)
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma focused on measuring lung cancer, angiogenesis inhibitor, chemotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • sanofi-aventis Australia & New Zealand administrative office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administraive Office
  • Sanofi-Aventis Admnistrative Office

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Placebo/Docetaxel

Aflibercept/Docetaxel

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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).
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).

Full Information

First Posted
September 19, 2007
Last Updated
May 4, 2016
Sponsor
Sanofi
Collaborators
Regeneron Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00532155
Brief Title
A Study of Aflibercept Versus Placebo in Patients With Second-Line Docetaxel for Locally Advanced or Metastatic Non-Small-Cell Lung Cancer
Acronym
VITAL
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
September 2007 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
October 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
Collaborators
Regeneron Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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). 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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Non Small Cell Lung
Keywords
lung cancer, angiogenesis inhibitor, chemotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
913 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo/Docetaxel
Arm Type
Experimental
Arm Description
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.
Arm Title
Aflibercept/Docetaxel
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Intervention Description
6 mg/kg Aflibercept administered intravenously (IV) over 1 hour once on Day 1, every 3 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo to Aflibercept administered intravenously (IV) over 1 hour once on Day 1, every 3 weeks.
Intervention Type
Drug
Intervention Name(s)
Docetaxel (Taxotere®)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone (pre- and post-medication for docetaxel)
Intervention Description
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).
Primary Outcome Measure Information:
Title
Overall Survival (OS)
Description
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.
Time Frame
Baseline to the date when 687 deaths occurred (26 January 2011)
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
Baseline to data cut-off (26 January 2011)
Title
Overall Response (OR) Rate as Per Response Evaluation Criteria in Solid Tumours (RECIST) Criteria
Description
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.
Time Frame
Baseline to data cut-off (26 January 2011)
Title
Health Related Quality of Life (HRQL) Assessed by the Lung Cancer Symptom Scale (LCSS)
Description
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).
Time Frame
Baseline (prior to first dose), at cycles 2 and 4 and at the end of study therapy.
Title
Health Related Quality of Life (HRQL) Assessed by the Average Symptom Burden Index (ASBI)
Description
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).
Time Frame
Baseline (prior to first dose), at cycles 2 and 4 and at the end of study therapy.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Sanofi-Aventis Administrative Office
City
Bridgewater
State/Province
New Jersey
ZIP/Postal Code
08807
Country
United States
Facility Name
Sanofi-Aventis Administrative Office
City
Buenos Aires
Country
Argentina
Facility Name
sanofi-aventis Australia & New Zealand administrative office
City
Macquarie Park
State/Province
New South Wales
Country
Australia
Facility Name
Sanofi-Aventis Administrative Office
City
Wien
Country
Austria
Facility Name
Sanofi-Aventis Administrative Office
City
Sao Paulo
Country
Brazil
Facility Name
Sanofi-Aventis Administrative Office
City
Sofia
Country
Bulgaria
Facility Name
Sanofi-Aventis Administrative Office
City
Laval
Country
Canada
Facility Name
Sanofi-Aventis Administrative Office
City
Santiago
Country
Chile
Facility Name
Sanofi-Aventis Administrative Office
City
Shangai
Country
China
Facility Name
Sanofi-Aventis Administrative Office
City
Praha
Country
Czech Republic
Facility Name
Sanofi-Aventis Administrative Office
City
Tallinn
Country
Estonia
Facility Name
Sanofi-Aventis Administrative Office
City
Helsinki
Country
Finland
Facility Name
Sanofi-Aventis Administrative Office
City
Paris
Country
France
Facility Name
Sanofi-Aventis Administrative Office
City
Berlin
Country
Germany
Facility Name
Sanofi-Aventis Administrative Office
City
Athens
Country
Greece
Facility Name
Sanofi-Aventis Administrative Office
City
Causeway Bay
Country
Hong Kong
Facility Name
Sanofi-Aventis Administrative Office
City
Budapest
Country
Hungary
Facility Name
Sanofi-Aventis Administrative Office
City
Mumbai
Country
India
Facility Name
Sanofi-Aventis Administrative Office
City
Milano
Country
Italy
Facility Name
Sanofi-Aventis Administrative Office
City
Seoul
Country
Korea, Republic of
Facility Name
Sanofi-Aventis Administrative Office
City
Kuala Lumpur
Country
Malaysia
Facility Name
Sanofi-Aventis Administrative Office
City
Gouda
Country
Netherlands
Facility Name
Sanofi-Aventis Administrative Office
City
Warszawa
Country
Poland
Facility Name
Sanofi-Aventis Administrative Office
City
Porto Salvo
Country
Portugal
Facility Name
Sanofi-Aventis Administrative Office
City
Bucuresti
Country
Romania
Facility Name
Sanofi-Aventis Administrative Office
City
Moscow
Country
Russian Federation
Facility Name
Sanofi-Aventis Administrative Office
City
Singapore
Country
Singapore
Facility Name
Sanofi-Aventis Administrative Office
City
Barcelona
Country
Spain
Facility Name
Sanofi-Aventis Administrative Office
City
Bromma
Country
Sweden
Facility Name
Sanofi-Aventis Administrative Office
City
Taipei
Country
Taiwan
Facility Name
Sanofi-Aventis Administraive Office
City
Istanbul
Country
Turkey
Facility Name
Sanofi-Aventis Admnistrative Office
City
Guildford Surrey
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
22965962
Citation
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.
Results Reference
result

Learn more about this trial

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

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