A Study of Aflibercept Versus Placebo in Patients With Second-Line Docetaxel for Locally Advanced or Metastatic Non-Small-Cell Lung Cancer
- Conditions
- CarcinomaNon Small Cell Lung
- Interventions
- Registration Number
- NCT00532155
- Lead Sponsor
- Sanofi
- 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)
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 913
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo/Docetaxel 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. Aflibercept/Docetaxel Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) 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. Aflibercept/Docetaxel 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 Docetaxel (Taxotere®) 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. Aflibercept/Docetaxel Docetaxel (Taxotere®) 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 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.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) 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.
- Secondary Outcome Measures
Name Time Method Health Related Quality of Life (HRQL) Assessed by the Lung Cancer Symptom Scale (LCSS) 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).
Health Related Quality of Life (HRQL) Assessed by the Average Symptom Burden Index (ASBI) 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).
Progression Free Survival (PFS) 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.Overall Response (OR) Rate as Per Response Evaluation Criteria in Solid Tumours (RECIST) Criteria 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.
Trial Locations
- Locations (4)
Sanofi-Aventis Administrative Office
🇨🇳Taipei, Taiwan
Sanofi-Aventis Administraive Office
🇹🇷Istanbul, Turkey
Sanofi-Aventis Admnistrative Office
🇬🇧Guildford Surrey, United Kingdom
sanofi-aventis Australia & New Zealand administrative office
🇦🇺Macquarie Park, New South Wales, Australia