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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
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
Secondary ID [1] 0 0
AVE0005
Secondary ID [2] 0 0
ARD6122
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms 0 0
Cancer of the Ovary 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal

Intervention/exposure
Study type
Interventional
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 Participants requiring more than 2 dose level reductions would be withdrawn from study treatment.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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

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
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.
Timepoint [1] 0 0
From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
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
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.
Timepoint [2] 0 0
From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Secondary outcome [1] 0 0
Number of Participants With a Clinical Benefit Response (CBR) as Per RECIST Based on the Analysis by the IRC
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.
Timepoint [1] 0 0
From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Secondary outcome [2] 0 0
Duration of Response (DR) Based on the Analysis by an Independent Review Committee (IRC)
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.
Timepoint [2] 0 0
From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Secondary outcome [3] 0 0
Tumor Marker Response Rate (TMRR) Based on the Gynecologic Cancer Intergroup (GCIG) Definition
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.
Timepoint [3] 0 0
From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Secondary outcome [4] 0 0
Time to Tumor Progression (TTP) as Per RECIST Based on the Analysis by the IRC
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.
Timepoint [4] 0 0
From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Secondary outcome [5] 0 0
Time to Tumor Marker (CA-125) Progression (TTMP)
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.
Timepoint [5] 0 0
From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Secondary outcome [6] 0 0
Number of Participants With Disease Progression Events for Progression-free Survival (PFS) Analysis by the IRC.
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.
Timepoint [6] 0 0
From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Secondary outcome [7] 0 0
Progression-free Survival (PFS) Time Based on Analysis by the IRC
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.
Timepoint [7] 0 0
From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Secondary outcome [8] 0 0
Overall Survival (OS) Time
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.
Timepoint [8] 0 0
From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Secondary outcome [9] 0 0
Overall Safety - Number of Participants With Adverse Events (AE)
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.
Timepoint [9] 0 0
up to 30+/-5 days after treatment discontinuation, or up to recovery or stabilization of a followed-up adverse event
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
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.
Timepoint [10] 0 0
On Day 1 of Cycle 1 (baseline) , and after Day 14 of Cycle 2

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
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2010
Sample size
Target
Accrual to date
Final
218
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Sanofi-Aventis Administrative Office - Macquarie Park
Recruitment postcode(s) [1] 0 0
- Macquarie Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New Jersey
Country [2] 0 0
Canada
State/province [2] 0 0
Laval
Country [3] 0 0
France
State/province [3] 0 0
Paris
Country [4] 0 0
Germany
State/province [4] 0 0
Berlin
Country [5] 0 0
Italy
State/province [5] 0 0
Milano
Country [6] 0 0
Netherlands
State/province [6] 0 0
Gouda
Country [7] 0 0
Portugal
State/province [7] 0 0
Porto Salvo
Country [8] 0 0
Spain
State/province [8] 0 0
Barcelona
Country [9] 0 0
Sweden
State/province [9] 0 0
Bromma
Country [10] 0 0
Switzerland
State/province [10] 0 0
Geneva

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Sanofi
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Regeneron Pharmaceuticals
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
ICD CSD
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

TypeCitations or Other Details
Journal Tew WP, Colombo N, Ray-Coquard I, Del Campo JM, Oz... [More Details]

Results are available at https://clinicaltrials.gov/study/NCT00327171