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

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ClinicalTrials.gov Identifier: NCT00574275
Recruitment Status : Terminated (Data Monitoring Committee concluded after a planned interim analysis that aflibercept added to gemcitabine would be unable to demonstrate improved survival)
First Posted : December 17, 2007
Results First Posted : September 25, 2012
Last Update Posted : June 7, 2016
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

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.


Condition or disease Intervention/treatment Phase
Pancreatic Neoplasm Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) Drug: Placebo Drug: Gemcitabine Phase 3

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 546 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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 Start Date : December 2007
Actual Primary Completion Date : October 2009
Actual Study Completion Date : November 2010


Arm Intervention/treatment
Placebo Comparator: Placebo and Gemcitabine
Participants with metastatic pancreatic cancer administered Placebo and 1000 mg/m^2 Gemcitabine.
Drug: Placebo
4 mg/kg was administered intravenously (IV) over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle

Drug: Gemcitabine
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.
Other Name: Gemzar

Experimental: Aflibercept and Gemcitabine
Participants with metastatic pancreatic cancer administered 4 mg/kg Aflibercept and 1000 mg/m^2 Gemcitabine.
Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
4 mg/kg was administered intravenously (IV) over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle.

Drug: Gemcitabine
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.
Other Name: Gemzar




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Progression Free Survival (PFS) Based on Response Evaluation Criteria in Solid Tumors [RECIST] Criteria [ Time Frame: From the first randomization until the end of study data cutoff date (approximately 2 years) ]

    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.


  2. Objective Response Rate (ORR) Assessed by the Investigators According to RECIST Criteria [ Time Frame: From the first randomization until the end of the study data cutoff date (approximately 2 years) ]

    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.


  3. Clinical Benefit [ Time Frame: From the first randomization until the end of the study data cutoff date (approximately 2 years) ]

    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.


  4. Safety-Number of Participants With Adverse Events (AE) [ Time Frame: up to 30 days after treatment discontinuation. SAEs and related AEs were followed till resolved or stabilized. ]
    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.

  5. Number of Participants With Anti-drug Antibodies [ Time Frame: Up to 90 days post last dose of study drug ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00574275


  Show 24 Study Locations
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Sciences & Operations Sanofi

Publications of Results:
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00574275     History of Changes
Other Study ID Numbers: EFC10547
EudraCT 2007-003476-19
First Posted: December 17, 2007    Key Record Dates
Results First Posted: September 25, 2012
Last Update Posted: June 7, 2016
Last Verified: May 2016
Keywords provided by Sanofi:
metastatic pancreatic cancer
angiogenesis inhibitor
gemcitabine
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Pancreatic Diseases
Digestive System Diseases
Endocrine System Diseases
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs