Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT00327171
Registration number
NCT00327171
Ethics application status
Date submitted
16/05/2006
Date registered
18/05/2006
Date last updated
7/06/2016
Titles & IDs
Public title
Study of AVE0005 (VEGF Trap) in Patients With Chemoresistant Advanced Ovarian Cancer
Query!
Scientific title
A Multicenter, Randomized, Double-blind, Parallel-arm, Two-stage Study of the Efficacy and Safety of AVE0005 (VEGF Trap) Administered Intravenously Every 2 Weeks in Patients With Platinum-resistant and topotecan-and/or Liposomal Doxorubicin-resistant Advanced Ovarian Cancer
Query!
Secondary ID [1]
0
0
AVE0005
Query!
Secondary ID [2]
0
0
ARD6122
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Neoplasms
0
0
Query!
Cancer of the Ovary
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Ovarian and primary peritoneal
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Treatment: Drugs - Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Experimental: Aflibercept 2.0 mg/kg - Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept.
Experimental: Aflibercept 4.0 mg/kg - Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept.
Treatment: Drugs: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Aflibercept 4.0 mg/kg administered intravenously (IV) over 1 hour once every 2 weeks.
Aflibercept could be reduced by 1 dose level ( to 2.0 mg/kg) or 2 dose levels (to 1.0 mg/kg) in case of uncontrolled hypertension or urinary protein >3.5 g/24 hours. Intrapatient dose escalation was not to be permitted. Participants requiring more than 2 dose level reductions would be withdrawn from study treatment.
Treatment: Drugs: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Aflibercept 2.0 mg/kg administered intravenously (IV) over 1 hour once every 2 weeks.
Aflibercept could be reduced by 1 dose level (to 1.0 mg/kg) or 2 dose levels (to 0.5 mg/kg) in case of uncontrolled hypertension or urinary protein >3.5 g/24 hours. Intrapatient dose escalation was not to be permitted. Participants requiring more than 2 dose level reductions would be withdrawn from study treatment.
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Number of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Based on the Analysis by an Independent Review Committee (IRC) - Simon's Cohort
Query!
Assessment method [1]
0
0
OR included Complete Response (CR) and Partial Response (PR). Per RECIST, CR was disappearance of all target or non-target lesions, or normalization of tumor marker levels (for non-target lesions) and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with baseline sum LD as reference.
Tumors were assessed by an independent third-party core imaging laboratory evaluating the chest, abdomen, and pelvis by Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans; and responses were confirmed by repeat tumor imaging 4-6 weeks later.
Query!
Timepoint [1]
0
0
From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Query!
Primary outcome [2]
0
0
Number of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Based on the Analysis by the IRC - Efficacy Evaluable Population
Query!
Assessment method [2]
0
0
OR included Complete Response (CR) and Partial Response (PR). Per RECIST, CR was disappearance of all target or non-target lesions, or normalization of tumor marker levels (for non-target lesions) and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with baseline sum LD as reference.
Tumors were assessed by an independent third-party core imaging laboratory evaluating the chest, abdomen, and pelvis by Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans; and responses were confirmed by repeat tumor imaging 4-6 weeks later.
Query!
Timepoint [2]
0
0
From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Query!
Secondary outcome [1]
0
0
Number of Participants With a Clinical Benefit Response (CBR) as Per RECIST Based on the Analysis by the IRC
Query!
Assessment method [1]
0
0
CBR was defined as having a Stable disease (SD) for >= 6 months or a confirmed OR (PR or CR). Based on RECIST:
SD was neither a sufficient shrinkage of the target lesions to qualify for PR nor sufficient increase to qualify for Progressive disease (PD), the persistence of non-target lesions or the maintenance of tumor marker level above the normal limits (for non-target lesions)
CR was the disappearance of all target or non-target lesions; and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with reference to the baseline sum LD.
Query!
Timepoint [1]
0
0
From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Query!
Secondary outcome [2]
0
0
Duration of Response (DR) Based on the Analysis by an Independent Review Committee (IRC)
Query!
Assessment method [2]
0
0
DR was defined as the time interval from the first documentation of CR or PR to the date of tumor progression (or disease progression) as determined by RECIST, or death from any cause, whichever was earlier.
Based on RECIST, progressive disease was at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, the appearance of one or more new target or non-target lesions, or the unequivocal progression of existing non-target lesions.
Query!
Timepoint [2]
0
0
From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Query!
Secondary outcome [3]
0
0
Tumor Marker Response Rate (TMRR) Based on the Gynecologic Cancer Intergroup (GCIG) Definition
Query!
Assessment method [3]
0
0
TMRR was the proportion of evaluable participants achieving a cancer antigen -125 (CA-125) response based on GCIG definition. A response to CA-125 occurred if after two elevated levels before therapy there was at least a 50% decrease in a post-treatment serum sample, which was confirmed by an independent sample collected 21 days or later that was =< 110% of the post-treatment serum sample.
Query!
Timepoint [3]
0
0
From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Query!
Secondary outcome [4]
0
0
Time to Tumor Progression (TTP) as Per RECIST Based on the Analysis by the IRC
Query!
Assessment method [4]
0
0
TTP was defined as the time interval measured from the date of randomization to the date of tumor progression as determined by RECIST. TTP was estimated from Kaplan-Meier curves.
For a participant who did not reach tumor progression during study, the censoring date was the date of the last valid tumor burden assessment or the date of study cut-off, whichever was earlier. If the participant had no valid post-baseline tumor burden assessment due to early termination, the censoring date was the date of randomization.
Query!
Timepoint [4]
0
0
From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Query!
Secondary outcome [5]
0
0
Time to Tumor Marker (CA-125) Progression (TTMP)
Query!
Assessment method [5]
0
0
TTMP was the time interval from the date of randomization to the date of tumor marker progression as was defined by GCIG for the evaluable participants. TTMP was estimated using Kaplan-Meier curves.
For a participant who did not reach tumor marker progression (TMP) during study, the censoring date was the date of the last valid tumor burden assessment or the date of study cut-off, whichever was earlier. If the participant had no valid post-baseline tumor burden assessment due to early termination, the censoring date was the date of randomization.
Query!
Timepoint [5]
0
0
From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Query!
Secondary outcome [6]
0
0
Number of Participants With Disease Progression Events for Progression-free Survival (PFS) Analysis by the IRC.
Query!
Assessment method [6]
0
0
PFS was as the time interval measured from the date of randomization to the date of tumor progression as determined by RECIST or death from any cause, whichever was earlier.
The number of participants with tumor/disease progression are reported. Participants who did not reach tumor progression during study, or had no valid post-baseline tumor burden assessment due to early termination, were censored in the PFS analysis.
Query!
Timepoint [6]
0
0
From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Query!
Secondary outcome [7]
0
0
Progression-free Survival (PFS) Time Based on Analysis by the IRC
Query!
Assessment method [7]
0
0
PFS was as the time interval measured from the date of randomization to the date of tumor progression as determined by RECIST or death from any cause, whichever was earlier. PFS was estimated using Kaplan-Meier curves.
For a participant who did not reach tumor progression during study, the censoring date was the date of the last valid tumor burden assessment or the date of study cut-off, whichever was earlier. If the participant had no valid post-baseline tumor burden assessment due to early termination, the censoring date was the date of randomization.
Query!
Timepoint [7]
0
0
From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Query!
Secondary outcome [8]
0
0
Overall Survival (OS) Time
Query!
Assessment method [8]
0
0
OS was the time interval between randomization and the date of death from any cause. OS was estimated using Kaplan-Meier curves
A participant was censored for the OS analysis if the participant were alive during the study. The censoring date was either at the date that the participant was last known to be alive or the date of study cut-off, whichever was earlier.
Query!
Timepoint [8]
0
0
From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Query!
Secondary outcome [9]
0
0
Overall Safety - Number of Participants With Adverse Events (AE)
Query!
Assessment method [9]
0
0
All AEs regardless of seriousness or relationship to study treatment, spanning from the first administration of study treatment until 30 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.
Query!
Timepoint [9]
0
0
up to 30+/-5 days after treatment discontinuation, or up to recovery or stabilization of a followed-up adverse event
Query!
Secondary outcome [10]
0
0
Participant's Assessment of Health Related Quality of Life (HRQL) Using a by Using the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) Questionnaire
Query!
Assessment method [10]
0
0
The FACT-O questionnaire consists of 38 scored questions (scored from 0-4) that address physical well-being, social/family well-being, emotional well-being, functional well-being and some additional concerns which relate specifically to ovarian cancer symptoms. For each question, higher scores reflect a better quality of life. The total FACT-O score ranges from 0-152, with 152 indicating the best outcome.
Query!
Timepoint [10]
0
0
On Day 1 of Cycle 1 (baseline) , and after Day 14 of Cycle 2
Query!
Eligibility
Key inclusion criteria
Participants who met the following criteria were eligible for the study.
- Histologically-confirmed ovarian epithelial (including fallopian tube and primary
peritoneal) adenocarcinoma.
- Prior treatment with at least 2 treatment regimens in the advanced disease treatment
setting
- 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
- Evidence of at least one unidimensional measurable tumor lesion by computed tomography
(CT) or magnetic resonance imaging (MRI) scan according to Response Evaluation
Criteria in Solid Tumors (RECIST) that has not been treated with surgery or radiation
therapy
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
- Diagnosis of any second malignancy within the last 5 years, except for adequately
treated basal cell or squamous cell skin cancer, or for in situ carcinoma of the
cervix uteri
- Prior treatment with a vascular endothelial growth factor (VEGF) or VEGF receptor
inhibitor
- More than 3 chemotherapy regimens in the advanced disease treatment setting
- Uncontrolled hypertension
The above information is not intended to contain all considerations relevant to potential
participation in a clinical trial.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
1/05/2006
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
1/03/2010
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
218
Query!
Recruitment in Australia
Recruitment state(s)
Query!
Recruitment hospital [1]
0
0
Sanofi-Aventis Administrative Office - Macquarie Park
Query!
Recruitment postcode(s) [1]
0
0
- Macquarie Park
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
New Jersey
Query!
Country [2]
0
0
Canada
Query!
State/province [2]
0
0
Laval
Query!
Country [3]
0
0
France
Query!
State/province [3]
0
0
Paris
Query!
Country [4]
0
0
Germany
Query!
State/province [4]
0
0
Berlin
Query!
Country [5]
0
0
Italy
Query!
State/province [5]
0
0
Milano
Query!
Country [6]
0
0
Netherlands
Query!
State/province [6]
0
0
Gouda
Query!
Country [7]
0
0
Portugal
Query!
State/province [7]
0
0
Porto Salvo
Query!
Country [8]
0
0
Spain
Query!
State/province [8]
0
0
Barcelona
Query!
Country [9]
0
0
Sweden
Query!
State/province [9]
0
0
Bromma
Query!
Country [10]
0
0
Switzerland
Query!
State/province [10]
0
0
Geneva
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Sanofi
Query!
Address
Query!
Country
Query!
Other collaborator category [1]
0
0
Commercial sector/Industry
Query!
Name [1]
0
0
Regeneron Pharmaceuticals
Query!
Address [1]
0
0
Query!
Country [1]
0
0
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
This study evaluated outcomes in participants with advanced ovarian epithelial adenocarcinoma
receiving aflibercept.
The primary objective was to compare the objective response rate of Aflibercept
(ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) 4.0 mg/kg and 2.0 mg/kg, administered
intravenously (IV) every 2 weeks with historical control in participants with advanced
ovarian epithelial (including fallopian tube and primary peritoneal) adenocarcinoma resistant
to platinum and topotecan and/or liposomal doxorubicin.
The secondary objectives was to further assess efficacy, safety, pharmacokinetics, potential
biological and pharmacogenomic markers of study drug activity, and health-related quality of
life.
This study employed an Independent Review Committee (IRC) for radiological tumor assessments.
For all tumor assessment-related efficacy variables, two analyses were performed: the primary
analysis was based on Independent Review Committee (IRC) reviewed data and the secondary
analysis was based on Investigator evaluation. If an endpoint was evaluated by the IRC, the
IRC reviewed data is reported for this study.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT00327171
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
ICD CSD
Query!
Address
0
0
Sanofi
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT00327171
Download to PDF