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

Carcinoma Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00532155
• Other study ID #: EFC10261
• Secondary ID: EudraCT 2007-000
• Status: Completed
• Phase: Phase 3
• First received: September 19, 2007
• Last updated: November 30, 2012
• Start date: September 2007
• Est. completion date: October 2011

Study information

• Verified date: January 2012
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationPoland: Ministry of HealthSpain: Spanish Agency of Medicines
• Study type: Interventional

Clinical 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).

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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 913
• Est. completion date: October 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Non Small Cell Lung

Intervention

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

Locations

Country	Name	City	State
Argentina	Sanofi-Aventis Administrative Office	Buenos Aires
Australia	sanofi-aventis Australia & New Zealand administrative office	Macquarie Park	New South Wales
Austria	Sanofi-Aventis Administrative Office	Wien
Brazil	Sanofi-Aventis Administrative Office	Sao Paulo
Bulgaria	Sanofi-Aventis Administrative Office	Sofia
Canada	Sanofi-Aventis Administrative Office	Laval
Chile	Sanofi-Aventis Administrative Office	Santiago
China	Sanofi-Aventis Administrative Office	Shangai
Czech Republic	Sanofi-Aventis Administrative Office	Praha
Estonia	Sanofi-Aventis Administrative Office	Tallinn
Finland	Sanofi-Aventis Administrative Office	Helsinki
France	Sanofi-Aventis Administrative Office	Paris
Germany	Sanofi-Aventis Administrative Office	Berlin
Greece	Sanofi-Aventis Administrative Office	Athens
Hong Kong	Sanofi-Aventis Administrative Office	Causeway Bay
Hungary	Sanofi-Aventis Administrative Office	Budapest
India	Sanofi-Aventis Administrative Office	Mumbai
Italy	Sanofi-Aventis Administrative Office	Milano
Korea, Republic of	Sanofi-Aventis Administrative Office	Seoul
Malaysia	Sanofi-Aventis Administrative Office	Kuala Lumpur
Netherlands	Sanofi-Aventis Administrative Office	Gouda
Poland	Sanofi-Aventis Administrative Office	Warszawa
Portugal	Sanofi-Aventis Administrative Office	Porto Salvo
Romania	Sanofi-Aventis Administrative Office	Bucuresti
Russian Federation	Sanofi-Aventis Administrative Office	Moscow
Singapore	Sanofi-Aventis Administrative Office	Singapore
Spain	Sanofi-Aventis Administrative Office	Barcelona
Sweden	Sanofi-Aventis Administrative Office	Bromma
Taiwan	Sanofi-Aventis Administrative Office	Taipei
Turkey	Sanofi-Aventis Administraive Office	Istanbul
United Kingdom	Sanofi-Aventis Admnistrative Office	Guildford Surrey
United States	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Bulgaria,  Canada,  Chile,  China,  Czech Republic,  Estonia,  Finland,  France,  Germany,  Greece,  Hong Kong,  Hungary,  India,  Italy,  Korea, Republic of,  Malaysia,  Netherlands,  Poland,  Portugal,  Romania,  Russian Federation,  Singapore,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline to the date when 687 deaths occurred (26 January 2011)	No
Secondary	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.	Baseline to data cut-off (26 January 2011)	No
Secondary	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.	Baseline to data cut-off (26 January 2011)	No
Secondary	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).	Baseline (prior to first dose), at cycles 2 and 4 and at the end of study therapy.	No
Secondary	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).	Baseline (prior to first dose), at cycles 2 and 4 and at the end of study therapy.	No