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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00532155




Registration number
NCT00532155
Ethics application status
Date submitted
19/09/2007
Date registered
20/09/2007
Date last updated
7/06/2016

Titles & IDs
Public title
A Study of Aflibercept Versus Placebo in Patients With Second-Line Docetaxel for Locally Advanced or Metastatic Non-Small-Cell Lung Cancer
Scientific 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
Secondary ID [1] 0 0
EudraCT 2007-000819-29
Secondary ID [2] 0 0
EFC10261
Universal Trial Number (UTN)
Trial acronym
VITAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma 0 0
Non Small Cell Lung 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Treatment: Drugs - Placebo
Treatment: Drugs - Docetaxel (Taxotere®)
Treatment: Drugs - Dexamethasone (pre- and post-medication for docetaxel)

Experimental: 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.

Placebo Comparator: 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.


Treatment: Drugs: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
6 mg/kg Aflibercept administered intravenously (IV) over 1 hour once on Day 1, every 3 weeks.

Treatment: Drugs: Placebo
Matching placebo to Aflibercept administered intravenously (IV) over 1 hour once on Day 1, every 3 weeks.

Treatment: Drugs: 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.

Treatment: Drugs: 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).

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline to the date when 687 deaths occurred (26 January 2011)
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline to data cut-off (26 January 2011)
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline to data cut-off (26 January 2011)
Secondary outcome [3] 0 0
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).
Timepoint [3] 0 0
Baseline (prior to first dose), at cycles 2 and 4 and at the end of study therapy.
Secondary outcome [4] 0 0
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).
Timepoint [4] 0 0
Baseline (prior to first dose), at cycles 2 and 4 and at the end of study therapy.

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
sanofi-aventis Australia & New Zealand administrative office - Macquarie Park
Recruitment postcode(s) [1] 0 0
- Macquarie Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New Jersey
Country [2] 0 0
Argentina
State/province [2] 0 0
Buenos Aires
Country [3] 0 0
Austria
State/province [3] 0 0
Wien
Country [4] 0 0
Brazil
State/province [4] 0 0
Sao Paulo
Country [5] 0 0
Bulgaria
State/province [5] 0 0
Sofia
Country [6] 0 0
Canada
State/province [6] 0 0
Laval
Country [7] 0 0
Chile
State/province [7] 0 0
Santiago
Country [8] 0 0
China
State/province [8] 0 0
Shangai
Country [9] 0 0
Czech Republic
State/province [9] 0 0
Praha
Country [10] 0 0
Estonia
State/province [10] 0 0
Tallinn
Country [11] 0 0
Finland
State/province [11] 0 0
Helsinki
Country [12] 0 0
France
State/province [12] 0 0
Paris
Country [13] 0 0
Germany
State/province [13] 0 0
Berlin
Country [14] 0 0
Greece
State/province [14] 0 0
Athens
Country [15] 0 0
Hong Kong
State/province [15] 0 0
Causeway Bay
Country [16] 0 0
Hungary
State/province [16] 0 0
Budapest
Country [17] 0 0
India
State/province [17] 0 0
Mumbai
Country [18] 0 0
Italy
State/province [18] 0 0
Milano
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Seoul
Country [20] 0 0
Malaysia
State/province [20] 0 0
Kuala Lumpur
Country [21] 0 0
Netherlands
State/province [21] 0 0
Gouda
Country [22] 0 0
Poland
State/province [22] 0 0
Warszawa
Country [23] 0 0
Portugal
State/province [23] 0 0
Porto Salvo
Country [24] 0 0
Romania
State/province [24] 0 0
Bucuresti
Country [25] 0 0
Russian Federation
State/province [25] 0 0
Moscow
Country [26] 0 0
Singapore
State/province [26] 0 0
Singapore
Country [27] 0 0
Spain
State/province [27] 0 0
Barcelona
Country [28] 0 0
Sweden
State/province [28] 0 0
Bromma
Country [29] 0 0
Taiwan
State/province [29] 0 0
Taipei
Country [30] 0 0
Turkey
State/province [30] 0 0
Istanbul
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Guildford Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sanofi
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Regeneron Pharmaceuticals
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00532155
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications