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
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Sanofi
- Enrollment
- 913
- Locations
- 4
- Primary Endpoint
- Overall Survival (OS)
Study Overview
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)
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
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.
Intervention: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) (Drug)
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.
Intervention: Docetaxel (Taxotere®) (Drug)
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.
Intervention: Dexamethasone (pre- and post-medication for docetaxel) (Drug)
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.
Intervention: Placebo (Drug)
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.
Intervention: Docetaxel (Taxotere®) (Drug)
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.
Intervention: Dexamethasone (pre- and post-medication for docetaxel) (Drug)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- 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.)
- 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.)
- Progression Free Survival (PFS)(Baseline to data cut-off (26 January 2011))
- Overall Response (OR) Rate as Per Response Evaluation Criteria in Solid Tumours (RECIST) Criteria(Baseline to data cut-off (26 January 2011))