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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00561470




Registration number
NCT00561470
Ethics application status
Date submitted
20/11/2007
Date registered
21/11/2007
Date last updated
28/09/2012

Titles & IDs
Public title
Aflibercept Versus Placebo in Combination With Irinotecan and 5-FU in the Treatment of Patients With Metastatic Colorectal Cancer After Failure of an Oxaliplatin Based Regimen
Scientific title
A Multinational, Randomized, Double-blind Study, Comparing the Efficacy of Aflibercept Once Every 2 Weeks Versus Placebo in Patients With Metastatic Colorectal Cancer (MCRC) Treated With Irinotecan / 5-FU Combination (FOLFIRI) After Failure of an Oxaliplatin Based Regimen
Secondary ID [1] 0 0
EudraCT 2007-000820-42
Secondary ID [2] 0 0
EFC10262
Universal Trial Number (UTN)
Trial acronym
VELOUR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Neoplasms 0 0
Neoplasm Metastasis 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Treatment: Drugs - FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)
Treatment: Drugs - FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)

Placebo Comparator: Placebo/FOLFIRI - Participants with Metastatic Colorectal Cancer administered Placebo followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) starting on Day 1 of a 2-week cycle until a treatment discontinuation criterion was met

Experimental: Aflibercept/FOLFIRI - Participants with Metastatic Colorectal Cancer administered Aflibercept followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) starting on Day 1 of a 2-week cycle until a treatment discontinuation criterion was met


Treatment: Drugs: Placebo
4 mg/kg of sterile aqueous buffered vehicle (pH 6.0) was administered intra venously (IV) over 1 hour on Day 1, every 2 weeks

Treatment: Drugs: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
4 mg/kg of Aflibercept was administered IV over 1 hour on Day 1, every 2 weeks.

Treatment: Drugs: FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)
The FOLFIRI regimen was initiated immediately after Placebo administration on Day 1
The FOLFIRI regimen included:
180 mg/m² Irinotecan (Campto®, Camptosar®) IV infusion over 90 minutes and dl leucovorin 400 mg/m² (200 mg/m² for the l-isomer form) IV infusion over 2 hours, followed by:
5-FU 400 mg/m² IV bolus given over 2-4 minutes, followed by:
5-FU 2400 mg/m² continuous IV infusion over 46-hours

Treatment: Drugs: FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)
The FOLFIRI regimen was initiated immediately after Aflibercept administration on Day 1
The FOLFIRI regimen included:
180 mg/m² Irinotecan (Campto®, Camptosar®) IV infusion over 90 minutes and dl leucovorin 400 mg/m² (200 mg/m² for the l-isomer form) IV infusion over 2 hours, followed by:
5-FU 400 mg/m² IV bolus given over 2-4 minutes, followed by:
5-FU 2400 mg/m² continuous IV infusion over 46-hours

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS) - Overall Survival was the time interval from the date of randomization to the date of death due to any cause. Once disease progression was documented, participants were followed every 2 months for survival status, until death or until the study cutoff date, whichever came first. The final data cutoff date for the analysis of OS was the date when 863 deaths had occurred (07 February 2011).
OS was estimated using the Kaplan-Meier method, and the Hazard Ratio was estimated using the Cox Proportional Hazard Model.
Timepoint [1] 0 0
From the date of the first randomization until the study data cut-off date, 07 February 2011 (approximately three years)
Secondary outcome [1] 0 0
Progression-free Survival (PFS) Assessed by Independent Review Committee (IRC) - PFS was the time interval from the date of randomization to the date of progression, or death from any cause if it occurs before tumor progression is documented. To evaluate disease progression, copies of all tumor imaging sets were systematically collected and assessed by the IRC.
PFS was analyzed using the Kaplan-Meier method, and the Hazard Ratio was estimated using the Cox Proportional Hazard Model.
The analysis for PFS was performed as planned when 561 deaths (OS events) had occurred.
Timepoint [1] 0 0
From the date of the first randomization until the occurrence of 561 OS events, 06 May 2010 (approximately 30 months)
Secondary outcome [2] 0 0
Overall Objective Response Rate (ORR) Based on the Tumor Assessment by the Independent Review Committee (IRC) as Per Response Evaluation Criteria in Solid Tumours (RECIST) Criteria - The overall ORR was the percentage of evaluable participants who achieved complete response [CR] or partial response [PR] according to RECIST criteria version 1.0.
CR reflected the disappearance of all tumor lesions (with no new tumors)
PR reflected a pre-defined reduction in tumor burden
Tumors were assessed by the IRC using Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans; and an observed response was confirmed by repeated imaging after 4 - 6 weeks.
Timepoint [2] 0 0
From the date of the first randomization until the study data cut-off date, 06 May 2010 (approximately 30 months)
Secondary outcome [3] 0 0
Number of Participants With Adverse Events (AE) - 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 [3] 0 0
From the date of the first randomization up to 30 days after the treatment discontinuation or until TEAE was resolved or stabilized
Secondary outcome [4] 0 0
Immunogenicity Assessment: Number of Participants With Positive Sample(s) in the Anti-drug Antibodies (ADA) Assay and in the Neutralizing Anti-drug Antibodies (NAb) Assay - Serum samples for immunogenicity assessment were analyzed using a bridging immunoassay to detect ADA. Positive samples in the ADA assay were further analyzed in the NAb assay using a validated, non-quantitative ligand binding assay.
Timepoint [4] 0 0
Baseline, every other treatment cycle, 30 days and 90 days after the last infusion of aflibercept/placebo

Eligibility
Key inclusion criteria
Participants who met the following main selection criteria were included in the study.



- Histologically or cytologically proven adenocarcinoma of the colon or rectum

- Metastatic disease that is not amenable to potentially curative treatment

- One and only one prior line of treatment for metastatic disease. This prior line
should be an oxaliplatin based chemotherapy (participants who relapse within 6 months
of completion of oxaliplatin based adjuvant chemotherapy are eligible)

- Prior treatment with bevacizumab is permitted.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior therapy with irinotecan

- Eastern Cooperative Oncology Group performance status >2

The above information is not intended to contain all considerations relevant to
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 administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Sanofi-Aventis Investigational Site Number 036004 - Hornsby
Recruitment hospital [2] 0 0
Sanofi-Aventis Investigational Site Number 036001 - Kingswood
Recruitment hospital [3] 0 0
Sanofi-Aventis Investigational Site Number 036002 - Kurralta Park
Recruitment hospital [4] 0 0
Sanofi-Aventis Investigational Site Number 036005 - Melbourne
Recruitment hospital [5] 0 0
Sanofi-Aventis Investigational Site Number 036003 - Melbourne
Recruitment hospital [6] 0 0
Sanofi-Aventis Investigational Site Number 036007 - Nedlands
Recruitment hospital [7] 0 0
Sanofi-Aventis Investigational Site Number 036006 - Subiaco
Recruitment postcode(s) [1] 0 0
2077 - Hornsby
Recruitment postcode(s) [2] 0 0
2747 - Kingswood
Recruitment postcode(s) [3] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [4] 0 0
3050 - Melbourne
Recruitment postcode(s) [5] 0 0
3128 - Melbourne
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment postcode(s) [7] 0 0
6008 - Subiaco
Recruitment outside Australia
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Northwood
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Sutton

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
Other collaborator category [2] 0 0
Other
Name [2] 0 0
NSABP Foundation Inc
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The main objective of the study was to evaluate the effectiveness of aflibercept (versus
placebo) in increasing the overall survival in participants with metastatic colorectal cancer
treated with FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) and that have previously
failed an oxaliplatin based treatment for metastatic disease.

The secondary objectives were to compare progression-free survival, to evaluate overall
response rate, to evaluate the safety profile, to assess immunogenicity of intravenous (IV)
aflibercept, and to assess pharmacokinetics of IV aflibercept in both treatment arms.
Trial website
https://clinicaltrials.gov/show/NCT00561470
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
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
Other publications