Aflibercept Compared to Placebo in Term of Efficacy in Patients Treated With Gemcitabine for Metastatic Pancreatic Cancer (VANILLA)

Sanofi

Status and phase: Terminated; Phase 3

Conditions: Pancreatic Neoplasm

Treatments: Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®); Drug: Placebo; Drug: Gemcitabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00574275

EFC10547

EudraCT 2007-003476-19

Details and patient eligibility

About

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.

Full 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

Enrollment: 546 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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546 participants in 2 patient groups, including a placebo group

Placebo and Gemcitabine

Placebo Comparator group

Description:

Participants with metastatic pancreatic cancer administered Placebo and 1000 mg/m\^2 Gemcitabine.

Treatment:

Drug: Gemcitabine

Drug: Placebo

Aflibercept and Gemcitabine

Experimental group

Description:

Participants with metastatic pancreatic cancer administered 4 mg/kg Aflibercept and 1000 mg/m\^2 Gemcitabine.

Treatment:

Drug: Gemcitabine

Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)