search
Back to results

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

Primary Purpose

Pancreatic Neoplasm

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Placebo
Gemcitabine
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Neoplasm focused on measuring metastatic pancreatic cancer, angiogenesis inhibitor, gemcitabine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo and Gemcitabine

Aflibercept and Gemcitabine

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.

Full Information

First Posted
December 14, 2007
Last Updated
May 4, 2016
Sponsor
Sanofi
Collaborators
Regeneron Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT00574275
Brief Title
Aflibercept Compared to Placebo in Term of Efficacy in Patients Treated With Gemcitabine for Metastatic Pancreatic Cancer
Acronym
VANILLA
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2016
Overall Recruitment Status
Terminated
Why Stopped
Data Monitoring Committee concluded after a planned interim analysis that aflibercept added to gemcitabine would be unable to demonstrate improved survival
Study Start Date
December 2007 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
November 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
Collaborators
Regeneron Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Neoplasm
Keywords
metastatic pancreatic cancer, angiogenesis inhibitor, gemcitabine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
546 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo and Gemcitabine
Arm Type
Placebo Comparator
Arm Description
Participants with metastatic pancreatic cancer administered Placebo and 1000 mg/m^2 Gemcitabine.
Arm Title
Aflibercept and Gemcitabine
Arm Type
Experimental
Arm Description
Participants with metastatic pancreatic cancer administered 4 mg/kg Aflibercept and 1000 mg/m^2 Gemcitabine.
Intervention Type
Drug
Intervention Name(s)
Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Intervention Description
4 mg/kg was administered intravenously (IV) over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
4 mg/kg was administered intravenously (IV) over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
Gemzar
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall Survival (OS)
Description
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)
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS) Based on Response Evaluation Criteria in Solid Tumors [RECIST] Criteria
Description
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)
Title
Objective Response Rate (ORR) Assessed by the Investigators According to RECIST Criteria
Description
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)
Title
Clinical Benefit
Description
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)
Title
Safety-Number of Participants With Adverse Events (AE)
Description
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.
Title
Number of Participants With Anti-drug Antibodies
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Sanofi-Aventis Administrative Office
City
Bridgewater
State/Province
New Jersey
ZIP/Postal Code
08807
Country
United States
Facility Name
Sanofi-Aventis Administrative Office
City
Buenos Aires
Country
Argentina
Facility Name
Sanofi-Aventis Administrative Office
City
Wien
Country
Austria
Facility Name
Sanofi-Aventis Administrative Office
City
Diegem
Country
Belgium
Facility Name
Sanofi-Aventis Administrative Office
City
Sofia
Country
Bulgaria
Facility Name
Sanofi-Aventis Administrative Office
City
Laval
Country
Canada
Facility Name
Sanofi-Aventis Administrative Office
City
Santiago
Country
Chile
Facility Name
Sanofi-Aventis Administrative Office
City
Santafe de Bogota
Country
Colombia
Facility Name
Sanofi-Aventis Administrative Office
City
Nikosia
Country
Cyprus
Facility Name
Sanofi-Aventis Administrative Office
City
Praha
Country
Czech Republic
Facility Name
Sanofi-Aventis Administrative Office
City
Paris
Country
France
Facility Name
Sanofi-Aventis Administrative Office
City
Berlin
Country
Germany
Facility Name
Sanofi-Aventis Administrative Office
City
Athens
Country
Greece
Facility Name
Sanofi-Aventis Administrative Office
City
Budapest
Country
Hungary
Facility Name
Sanofi-Aventis Administrative Office
City
Mumbai
Country
India
Facility Name
Sanofi-Aventis Administrative Office
City
Milano
Country
Italy
Facility Name
Sanofi-Aventis Administrative Office
City
Mexico
Country
Mexico
Facility Name
Sanofi-Aventis Administrative Office
City
Warszawa
Country
Poland
Facility Name
Sanofi-Aventis Administrative Office
City
Puerto Rico
Country
Puerto Rico
Facility Name
Sanofi-Aventis Administrative Office
City
Bucuresti
Country
Romania
Facility Name
Sanofi-Aventis Administrative Office
City
Moscow
Country
Russian Federation
Facility Name
Sanofi-Aventis Administrative Office
City
Brastislava
Country
Slovakia
Facility Name
Sanofi-Aventis Administrative Office
City
Barcelona
Country
Spain
Facility Name
Sanofi-Aventis Administrative Office
City
Geneva
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
23642329
Citation
Rougier P, Riess H, Manges R, Karasek P, Humblet Y, Barone C, Santoro A, Assadourian S, Hatteville L, Philip PA. Randomised, placebo-controlled, double-blind, parallel-group phase III study evaluating aflibercept in patients receiving first-line treatment with gemcitabine for metastatic pancreatic cancer. Eur J Cancer. 2013 Aug;49(12):2633-42. doi: 10.1016/j.ejca.2013.04.002. Epub 2013 Apr 30.
Results Reference
result

Learn more about this trial

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

We'll reach out to this number within 24 hrs