AVE0005 (VEGF Trap) in Patients With Recurrent Symptomatic Malignant Ascites

This study has been completed.
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00396591
First received: November 6, 2006
Last updated: January 9, 2013
Last verified: July 2011
  Purpose

The primary objective of this study was to compare the time between paracenteses before and after administration of Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) in ovarian cancer participants with symptomatic malignant ascites.

The secondary objectives were to further assess efficacy and safety of Aflibercept treatment, and the exploratory objectives were to assess pharmacokinetics, immunogenicity and health-related quality of life.


Condition Intervention Phase
Ovarian Neoplasms
Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, Single-arm Study of the Efficacy and Safety of Intravenous AVE0005 (VEGF Trap) Administered Every 2 Weeks in Advanced Ovarian Cancer Patients With Recurrent Symptomatic Malignant Ascites

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Percentage of Participants With a Repeat Paracentesis Response (RPR) [ Time Frame: up to 2 years post-registration ] [ Designated as safety issue: No ]

    RPR was defined as at least a two-fold increase in the time to repeat paracentesis (TRP) as compared to the average duration of the 2 intervals between the 3 most recent paracenteses prior to study registration (ie, the baseline interval of paracentesis).

    Percentage of participants with a repeat paracentesis response were the number of participants with RPR / number of total participants * 100.



Secondary Outcome Measures:
  • Time to Repeat Paracentesis (TRP) [ Time Frame: up to 6 months from registration ] [ Designated as safety issue: No ]
    TRP is the number of days between the date of registration and the date of the first postregistration paracentesis. Median TRP was estimated from Kaplan-Meier curves. For participants who did not undergo a postregistration paracentesis while on study, TRP was censored at the end of the treatment period (last dose + 1 cycle), at the last visit known without repeat paracentesis, at 6 months postregistration, or at death, whichever was earlier.

  • 60-day Frequency of Paracentesis (FOP) [ Time Frame: up to 60 days post-registration ] [ Designated as safety issue: No ]
    FOP was the total number of paracenteses performed within the first 60 days postregistration. For participants who had withdrawn after registration but prior to the 60-day cutoff date, the withdrawal would have been regarded as a paracentesis event and the 60-day FOP normalized and calculated as the nearest integer of the value corresponding to 60 × number of paracenteses / x, where x represents the number of days on study.

  • Progression-free Survival (PFS) Time [ Time Frame: up to 6 months post-registration ] [ Designated as safety issue: No ]

    According to the Response Evaluation Criteria in Solid Tumors [RECIST], progression was at least a 20% increase in the sum of the longest diameter (LD) of tumors, compared to smallest sum LD recorded since treatment started, or the appearance of one or more new tumors.

    PFS time was interval from the date of registration to the date of tumor progression or death from any cause, whichever was earlier. Median PFS time was estimated from Kaplan-Meier Plots.

    If participants were alive and progression-free at 6 months postregistration, they were censored for PFS.


  • Overall Survival (OS) Time [ Time Frame: up to 6 months post-registration ] [ Designated as safety issue: No ]
    OS time was the time interval between the date of registration to the date of death from any cause. Median OS was estimated from Kaplan-Meier curves. Participants who died after efficacy data cutoff date (6 months postregistration) were censored at the data cutoff date.

  • Number of Participants With a Positive Anti-drug Antibody Response [ Time Frame: up to 60 days after the last dose of treatment ] [ Designated as safety issue: No ]

    Anti-drug antibodies in participant's serum were measured using 2 different methods

    • an Enzyme Linked Immunosorbent Assay (ELISA) in which the lower limit of detection (LLOD) was 238.4 ng/mL; and
    • an Electrochemiluminescence-based, Bridging Assay in which the validated LLOD 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.

    Participants with detectable anti-drug antibodies by either method were considered to have a positive anti-drug antibody response.


  • Safety - Number of Participants With Adverse Events (AE) [ Time Frame: up to 60 days after last dose of treatment (approximately 2 years), or until TEAE was resolved or stabilized ] [ Designated as safety issue: Yes ]
    All AEs regardless of seriousness or relationship to study treatment, spanning from the first administration of study treatment until 60 days after the last administration of study treatment, were recorded, and followed until resolution or stabilization. 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.


Enrollment: 16
Study Start Date: October 2006
Study Completion Date: November 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aflibercept
Participants with advanced ovarian epithelial cancer (including fallopian tube and primary peritoneal adenocarcinoma) treated with Aflibercept every 2 weeks until a criterion for treatment discontinuation was met
Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
4.0 mg/kg administered intravenously (IV) once every 2 weeks

Detailed Description:

The study consisted of:

  • A 30-day screening phase prior to Day 1
  • Day 1 registration and pre-treatment paracentesis
  • Aflibercept administration within 1-day of registration
  • Two-week study treatment cycles (for efficacy data, the cut-off date was 6 months post-registration
  • A 60-day post-treatment follow-up phase

During the study, participants were treated with Aflibercept study treatment through the duration of the study unless they met one the following criteria for discontinuation:

  • Participant (or legal representative) chose to withdraw from treatment
  • The investigator or sponsor thought that continuation of the study would be detrimental to the participants well-being
  • Participant had intercurrent illness that prevented further administration of investigational product (IP)
  • Participant had more than 2 IP dose reductions
  • Participant had unacceptable adverse events (AEs)
  • Participant had arterial thromboembolic events, including cerebrovascular accidents, myocardial infarctions, transient ischemic attacks, new onset angina, or worsening of preexisting angina
  • Participant required surgical intervention for intestinal obstruction or gastrointestinal perforation
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Participants that met the following criteria were eligible.

Inclusion Criteria:

  • Symptomatic malignant ascites resulting from advanced ovarian epithelial cancer (including fallopian tube and primary peritoneal adenocarcinoma) that required at least 3 previous therapeutic paracenteses at a frequency of 1 to 4 paracenteses per month for management.
  • Platinum resistant disease defined by relapse or progression of disease during or after treatment, or drug intolerance.
  • Topotecan- and/or liposomal doxorubicin-resistant disease defined by relapse or progression of disease during or after treatment, or drug intolerance.

Exclusion Criteria:

  • Peritoneovenous or other type of shunt that was placed for the management of ascites
  • Prior treatment with a VEGF or VEGF receptor inhibitor
  • Uncontrolled hypertension

The above information is not intended to contain all considerations relevant to participation in a clinical trial.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00396591

Locations
United States, New Jersey
Sanofi-Aventis Administrative Office
Bridgewater, New Jersey, United States, 08807
Italy
Sanofi-Aventis Administrative Office
Milano, Italy
Sweden
Sanofi-Aventis Administrative Office
Bromma, Sweden
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
Study Director: ICD Sanofi
  More Information

No publications provided by Sanofi

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00396591     History of Changes
Other Study ID Numbers: ARD6772, EUDRACT: 2006-000604-16
Study First Received: November 6, 2006
Results First Received: August 17, 2012
Last Updated: January 9, 2013
Health Authority: United States: Food and Drug Administration
Italy: Ethics Committee
Sweden: Medical Products Agency

Keywords provided by Sanofi:
Ovarian cancer
malignant ascites
angiogenesis
angiogenesis inhibition
VEGF-Trap fusion recombinant protein

Additional relevant MeSH terms:
Ascites
Neoplasms
Ovarian Neoplasms
Pathologic Processes
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders

ClinicalTrials.gov processed this record on April 17, 2014