A Multinational, Randomized, Double-blind Study, Comparing the Efficacy of Aflibercept Once Every 2 Weeks Versus Placebo in Patients Treated With Gemcitabine for Metastatic Pancreatic Cancer
Trial Snapshot
- Phase
- Phase 3
- Status
- Terminated
- Sponsor
- Sanofi
- Enrollment
- 546
- Locations
- 1
- Primary Endpoint
- Overall Survival (OS)
Study Overview
Brief Summary
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.
Detailed Description
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 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
- •Cytologically or histologically confirmed evidence of epithelial cancer (adenocarcinoma) of the exocrine pancreas
- •Metastatic disease
- •No prior chemotherapy for pancreatic disease
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- •Adequate renal, liver and bone marrow functions
Exclusion Criteria
- •Less than 42 days elapsed from prior major surgery (28 days from other prior surgery) to the time of randomization
- •Prior treatment with anti-VEGF or VEGF-Receptor-inhibitors
- •Uncontrolled hypertension
- •Pregnancy or breastfeeding
- •Participant with reproductive potential (M/F) without effective method of contraception
- •The above information is not intended to contain all considerations relevant to potential participation in a clinical trial.
Arms & Interventions
Placebo and Gemcitabine
Participants with metastatic pancreatic cancer administered Placebo and 1000 mg/m^2 Gemcitabine.
Intervention: Placebo (Drug)
Placebo and Gemcitabine
Participants with metastatic pancreatic cancer administered Placebo and 1000 mg/m^2 Gemcitabine.
Intervention: Gemcitabine (Drug)
Aflibercept and Gemcitabine
Participants with metastatic pancreatic cancer administered 4 mg/kg Aflibercept and 1000 mg/m^2 Gemcitabine.
Intervention: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) (Drug)
Aflibercept and Gemcitabine
Participants with metastatic pancreatic cancer administered 4 mg/kg Aflibercept and 1000 mg/m^2 Gemcitabine.
Intervention: Gemcitabine (Drug)
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: From the first randomization until the end of study data cutoff date (approximately 2 years)
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.
Secondary Outcomes
- Number of Participants With Anti-drug Antibodies(Up to 90 days post last dose of study drug)
- Progression Free Survival (PFS) Based on Response Evaluation Criteria in Solid Tumors [RECIST] Criteria(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(From the first randomization until the end of the study data cutoff date (approximately 2 years))
- Clinical Benefit(From the first randomization until the end of the study data cutoff date (approximately 2 years))
- Safety-Number of Participants With Adverse Events (AE)(up to 30 days after treatment discontinuation. SAEs and related AEs were followed till resolved or stabilized.)