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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 Participants requiring more than 2 dose level reductions would be withdrawn from study treatment.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
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
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
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)
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
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
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)
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.
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
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
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)
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
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
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Regeneron Pharmaceuticals
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/study/NCT00327171
Trial related presentations / publications
Tew WP, Colombo N, Ray-Coquard I, Del Campo JM, Oza A, Pereira D, Mammoliti S, Matei D, Scambia G, Tonkin K, Shun Z, Sternas L, Spriggs DR. Intravenous aflibercept in patients with platinum-resistant, advanced ovarian cancer: results of a randomized, double-blind, phase 2, parallel-arm study. Cancer. 2014 Feb 1;120(3):335-43. doi: 10.1002/cncr.28406. Epub 2013 Oct 11.
Public notes

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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00327171