The main objective of the study was to evaluate the effectiveness of aflibercept treatment by comparison to placebo in increasing the overall survival (OS) in participants with metastatic pancreatic cancer, treated with gemcitabine. The secondary objectives were to evaluate progression free survival, clinical benefit, overall response, safety and immunogenicity of aflibercept, in the two treatment arms (Arm 1: Aflibercept and Gemcitabine; Arm 2: Placebo and Gemcitabine). The study included an interim analysis of OS. In accordance with the study protocol, an interim analysis was performed for the purpose of futility and overwhelming efficacy. On the basis of the interim analysis, the Data Monitoring Committee (DMC) recommended that this study be terminated for futility based on predefined boundary rules.
The study included: * A screening visit of up to 21 days prior to randomization * Randomization at baseline * A Treatment period (initiated within 3 days of randomization), which included 28-day treatment cycles in both arms until predefined treatment discontinuation criteria were met * A follow-up visit 30 days after discontinuation of treatment, * A post study treatment follow-up period until death or the study cutoff date. The criteria for treatment discontinuation were: * Participant (or legal representative) chose to withdraw from treatment * The investigator thought that continuation of the study would be detrimental to the participants well-being, such as: * Disease progression * Unacceptable AEs not manageable by symptomatic therapy, dose delay, or dose modification * Intercurrent illness that prevented further administration of study treatment * Noncompliance with the study protocol * Participant was lost to follow-up * Unblinding of the participant's investigational treatment
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
546
4 mg/kg was administered intravenously (IV) over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle.
4 mg/kg was administered intravenously (IV) over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle
1000 mg/m\^2 administered IV over 30 minutes on Days 1, 8, 15, and 22 of Cycle 1 (28 days), and then Days 1, 8, and 15 of subsequent 28-day cycles.
Sanofi-Aventis Administrative Office
Bridgewater, New Jersey, United States
Sanofi-Aventis Administrative Office
Buenos Aires, Argentina
Sanofi-Aventis Administrative Office
Vienna, Austria
Sanofi-Aventis Administrative Office
Diegem, Belgium
Sanofi-Aventis Administrative Office
Sofia, Bulgaria
Sanofi-Aventis Administrative Office
Laval, Canada
Sanofi-Aventis Administrative Office
Santiago, Chile
Sanofi-Aventis Administrative Office
Bogotá, Colombia
Sanofi-Aventis Administrative Office
Nicosia, Cyprus
Sanofi-Aventis Administrative Office
Prague, Czechia
...and 14 more locations
Overall Survival (OS)
OS is the time interval from the date of randomization to the date of death due to any cause. If death was not observed during the study, data on OS were censored at the earlier of the last date participant was known to be alive, or the study data cutoff date (11 September 2009). OS time was estimated from Kaplan-Meier Plots.
Time frame: From the first randomization until the end of study data cutoff date (approximately 2 years)
Progression Free Survival (PFS) Based on Response Evaluation Criteria in Solid Tumors [RECIST] Criteria
PFS was the time interval from the date of registration to the date of progression, or death from any cause if it occurs before tumor progression is documented. Tumor progression was assessed using RECIST criteria, by which progression was a pre-defined increase in the size of existing tumors or appearance of one or more new tumors. If a participant did not progress or die, the progression was censored to the date of the last valid tumor assessment or data cut-off, whichever was earlier. Median PFS time was estimated from Kaplan-Meier Plots.
Time frame: From the first randomization until the end of study data cutoff date (approximately 2 years)
Objective Response Rate (ORR) Assessed by the Investigators According to RECIST Criteria
Objective response (OR) included complete response \[CR\] and partial response \[PR\]. OR was to be assessed by the Investigators according to RECIST criteria, and confirmed by repeating tumor imaging at least 4 weeks after the first radiological documentation of response. CR would reflect the disappearance of all tumor lesions and PR would reflect a defined reduction of tumor burden. However, OR analysis was not performed, as the study was terminated due to futility.
Time frame: From the first randomization until the end of the study data cutoff date (approximately 2 years)
Clinical Benefit
Clinical benefit was to be assessed in all participants by time to symptom worsening (TTSW), evaluated from the time of randomization to symptom worsening, as well as by improvement in tumor related symptoms. However, this analysis was not performed, as the study was terminated due to futility.
Time frame: From the first randomization until the end of the study data cutoff date (approximately 2 years)
Safety-Number of Participants With Adverse Events (AE)
All AEs regardless of seriousness or relationship to study treatment, spanning from the signature of informed consent until 30 days after the last administration of study treatment, were recorded. The number of participants with all treatment emergent adverse events (TEAE), serious adverse events (SAE), TEAE leading to death, and TEAE leading to permanent treatment discontinuation are reported.
Time frame: up to 30 days after treatment discontinuation. SAEs and related AEs were followed till resolved or stabilized.
Number of Participants With Anti-drug Antibodies
Anti-drug antibodies in the participants blood sample were detected using a validated immunoassay. The validated lower limit of detection (LLOD) for the assay was about 5.4 ng/mL in the absence of aflibercept and about 25.2 ng/mL in the presence of 20 μg/mL of aflibercept.
Time frame: Up to 90 days post last dose of study drug
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.