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

Colorectal Neoplasms Clinical Trial

— VELOUR  

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00561470
• Other study ID #: EFC10262
• Secondary ID: EudraCT 2007-000
• Status: Completed
• Phase: Phase 3
• First received: November 20, 2007
• Last updated: September 27, 2012
• Start date: November 2007
• Est. completion date: June 2012

Study information

• Verified date: March 2012
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationSpain: Spanish Agency of MedicinesAustralia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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.

Description:

Participants were

• randomized at baseline (treatment was initiated with 3 days of randomization)

• administered treatment in cycles of 14-days till a study withdrawal criterion was met

• followed up 30 days after discontinuation of treatment, and every 8 weeks until death or end of study.

The criteria for discontinuation of study treatment for a participant are:

• participant (or legal representative) chose to withdraw from treatment

• the investigator thought that continuation of the study would be detrimental to the participants well-being due to

• disease progression

• unacceptable AEs

• intercurrent illnesses

• non-compliance to the study protocol

• participant was lost to follow-up

• participant was unblinded for the investigational treatment

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1226
• Est. completion date: June 2012
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Inclusion Criteria:

• 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.

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Neoplasm Metastasis
• Neoplasms

Intervention

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

Locations

Country	Name	City	State
Argentina	Sanofi-Aventis Investigational Site Number 032003	Bahia Blanca
Argentina	Sanofi-Aventis Investigational Site Number 032006	Buenos Aires
Argentina	Sanofi-Aventis Investigational Site Number 032005	Ciudad De Buenos Aires
Argentina	Sanofi-Aventis Investigational Site Number 032007	Salta
Australia	Sanofi-Aventis Investigational Site Number 036004	Hornsby
Australia	Sanofi-Aventis Investigational Site Number 036001	Kingswood
Australia	Sanofi-Aventis Investigational Site Number 036002	Kurralta Park
Australia	Sanofi-Aventis Investigational Site Number 036003	Melbourne
Australia	Sanofi-Aventis Investigational Site Number 036005	Melbourne
Australia	Sanofi-Aventis Investigational Site Number 036007	Nedlands
Australia	Sanofi-Aventis Investigational Site Number 036006	Subiaco
Austria	Sanofi-Aventis Investigational Site Number 040001	Wien
Belgium	Sanofi-Aventis Investigational Site Number 056006	Bonheiden
Belgium	Sanofi-Aventis Investigational Site Number 056002	Bruxelles
Belgium	Sanofi-Aventis Investigational Site Number 056004	Bruxelles
Belgium	Sanofi-Aventis Investigational Site Number 056007	Bruxelles
Belgium	Sanofi-Aventis Investigational Site Number 056001	Gent
Belgium	Sanofi-Aventis Investigational Site Number 056005	Haine-Saint-Paul
Belgium	Sanofi-Aventis Investigational Site Number 056003	Leuven
Brazil	Sanofi-Aventis Investigational Site Number 076002	Porto Alegre
Brazil	Sanofi-Aventis Investigational Site Number 076004	Porto Alegre
Brazil	Sanofi-Aventis Investigational Site Number 076005	Porto Alegre
Brazil	Sanofi-Aventis Investigational Site Number 076003	Rio De Janeiro
Brazil	Sanofi-Aventis Investigational Site Number 076008	Rio De Janeiro
Brazil	Sanofi-Aventis Investigational Site Number 076001	Santo Andre
Brazil	Sanofi-Aventis Investigational Site Number 076006	Sao Paulo
Brazil	Sanofi-Aventis Investigational Site Number 076007	Sao Paulo
Chile	Sanofi-Aventis Investigational Site Number 152001	Santiago
Chile	Sanofi-Aventis Investigational Site Number 152002	Santiago
Chile	Sanofi-Aventis Investigational Site Number 152003	Santiago
Chile	Sanofi-Aventis Investigational Site Number 152005	Santiago
Chile	Sanofi-Aventis Investigational Site Number 152004	Viña Del Mar
Czech Republic	Sanofi-Aventis Investigational Site Number 203001	Brno
Czech Republic	Sanofi-Aventis Investigational Site Number 203002	Brno
Czech Republic	Sanofi-Aventis Investigational Site Number 203004	Praha 5
Denmark	Sanofi-Aventis Investigational Site Number 208003	Ålborg
Denmark	Sanofi-Aventis Investigational Site Number 208001	Odense C
Estonia	Sanofi-Aventis Investigational Site Number 233002	Tallinn
Estonia	Sanofi-Aventis Investigational Site Number 233001	Tartu
France	Sanofi-Aventis Investigational Site Number 250002	Brest
France	Sanofi-Aventis Investigational Site Number 250004	Clichy Cx
France	Sanofi-Aventis Investigational Site Number 250005	La Roche Sur Yon
France	Sanofi-Aventis Investigational Site Number 250001	Lyon Cedex 03
France	Sanofi-Aventis Investigational Site Number 250003	Paris
Germany	Sanofi-Aventis Investigational Site Number 276003	Aschaffenburg
Germany	Sanofi-Aventis Investigational Site Number 276002	Essen
Germany	Sanofi-Aventis Investigational Site Number 276001	Halle / Saale
Germany	Sanofi-Aventis Investigational Site Number 276004	Magdeburg
Germany	Sanofi-Aventis Investigational Site Number 276005	Magdeburg
Germany	Sanofi-Aventis Investigational Site Number 276006	München
Greece	Sanofi-Aventis Investigational Site Number 300004	Athens
Greece	Sanofi-Aventis Investigational Site Number 300005	Athens
Greece	Sanofi-Aventis Investigational Site Number 300001	Heraklion
Greece	Sanofi-Aventis Investigational Site Number 300002	Ilion, Athens
Greece	Sanofi-Aventis Investigational Site Number 300003	Patras
Italy	Sanofi-Aventis Investigational Site Number 380007	Ancona
Italy	Sanofi-Aventis Investigational Site Number 380005	Aviano
Italy	Sanofi-Aventis Investigational Site Number 380004	Candiolo
Italy	Sanofi-Aventis Investigational Site Number 380003	Genova
Italy	Sanofi-Aventis Investigational Site Number 380001	Milano
Italy	Sanofi-Aventis Investigational Site Number 380002	Milano
Italy	Sanofi-Aventis Investigational Site Number 380008	Rozzano
Italy	Sanofi-Aventis Investigational Site Number 380006	San Giovanni Rotondo
Korea, Republic of	Sanofi-Aventis Investigational Site Number 410001	Goyang
Korea, Republic of	Sanofi-Aventis Investigational Site Number 410002	Seoul
Korea, Republic of	Sanofi-Aventis Investigational Site Number 410003	Seoul
Korea, Republic of	Sanofi-Aventis Investigational Site Number 410004	Seoul
Korea, Republic of	Sanofi-Aventis Investigational Site Number 410005	Seoul
Netherlands	Sanofi-Aventis Investigational Site Number 528004	Amsterdam
Netherlands	Sanofi-Aventis Investigational Site Number 528001	Blaricum
Netherlands	Sanofi-Aventis Investigational Site Number 528005	Breda
Netherlands	Sanofi-Aventis Investigational Site Number 528002	Rotterdam
Netherlands	Sanofi-Aventis Investigational Site Number 528003	Sittard-Geleen
New Zealand	Sanofi-Aventis Investigational Site Number 554009	Auckland
New Zealand	Sanofi-Aventis Investigational Site Number 554010	Christchurch
Norway	Sanofi-Aventis Investigational Site Number 578002	Bergen
Norway	Sanofi-Aventis Investigational Site Number 578001	Oslo
Norway	Sanofi-Aventis Investigational Site Number 578003	Stavanger
Poland	Sanofi-Aventis Investigational Site Number 616005	Czestochowa
Poland	Sanofi-Aventis Investigational Site Number 616004	Elblag
Poland	Sanofi-Aventis Investigational Site Number 616007	Krakow
Poland	Sanofi-Aventis Investigational Site Number 616003	Lodz
Poland	Sanofi-Aventis Investigational Site Number 616002	Poznan
Poland	Sanofi-Aventis Investigational Site Number 616006	Rybnik
Poland	Sanofi-Aventis Investigational Site Number 616001	Wroclaw
Puerto Rico	Sanofi-Aventis Investigational Site Number 630001	San Juan
Romania	Sanofi-Aventis Investigational Site Number 642004	Alba Iulia
Romania	Sanofi-Aventis Investigational Site Number 642007	Bucharest
Romania	Sanofi-Aventis Investigational Site Number 642001	Bucuresti
Romania	Sanofi-Aventis Investigational Site Number 642002	Bucuresti
Romania	Sanofi-Aventis Investigational Site Number 642003	Cluj Napoca
Romania	Sanofi-Aventis Investigational Site Number 642006	Iasi
Romania	Sanofi-Aventis Investigational Site Number 642005	Suceava
Russian Federation	Sanofi-Aventis Investigational Site Number 643001	Moscow
Russian Federation	Sanofi-Aventis Investigational Site Number 643002	Moscow
Russian Federation	Sanofi-Aventis Investigational Site Number 643006	Moscow
Russian Federation	Sanofi-Aventis Investigational Site Number 643003	Saint-Petersburg
Russian Federation	Sanofi-Aventis Investigational Site Number 643004	St-Petersburg
Russian Federation	Sanofi-Aventis Investigational Site Number 643007	St-Petersburg
South Africa	Sanofi-Aventis Investigational Site Number 710004	Cape Town
South Africa	Sanofi-Aventis Investigational Site Number 710005	Durban
South Africa	Sanofi-Aventis Investigational Site Number 710008	Durban
South Africa	Sanofi-Aventis Investigational Site Number 710001	Parktown
South Africa	Sanofi-Aventis Investigational Site Number 710006	Port Elizabeth
South Africa	Sanofi-Aventis Investigational Site Number 710003	Pretoria
South Africa	Sanofi-Aventis Investigational Site Number 710007	Pretoria
Spain	Sanofi-Aventis Investigational Site Number 724002	Barakaldo
Spain	Sanofi-Aventis Investigational Site Number 724001	Barcelona
Spain	Sanofi-Aventis Investigational Site Number 724005	Barcelona
Spain	Sanofi-Aventis Investigational Site Number 724003	Madrid
Spain	Sanofi-Aventis Investigational Site Number 724006	Madrid
Spain	Sanofi-Aventis Investigational Site Number 724007	Reus
Sweden	Sanofi-Aventis Investigational Site Number 752002	Stockholm
Sweden	Sanofi-Aventis Investigational Site Number 752003	Sundsvall
Sweden	Sanofi-Aventis Investigational Site Number 752001	Uppsala
Turkey	Sanofi-Aventis Investigational Site Number 792005	Adana
Turkey	Sanofi-Aventis Investigational Site Number 792001	Ankara
Turkey	Sanofi-Aventis Investigational Site Number 792004	Ankara
Turkey	Sanofi-Aventis Investigational Site Number 792002	Izmir
Turkey	Sanofi-Aventis Investigational Site Number 792003	Kayseri
Ukraine	Sanofi-Aventis Investigational Site Number 804005	Dnipropetrovsk
Ukraine	Sanofi-Aventis Investigational Site Number 804004	Donetsk
Ukraine	Sanofi-Aventis Investigational Site Number 804006	Kharkiv
Ukraine	Sanofi-Aventis Investigational Site Number 804002	Kharkov
United Kingdom	Sanofi-Aventis Investigational Site Number 826001	Aberdeen
United Kingdom	Sanofi-Aventis Investigational Site Number 826010	Bournemouth
United Kingdom	Sanofi-Aventis Investigational Site Number 826009	Dudley
United Kingdom	Sanofi-Aventis Investigational Site Number 826004	London
United Kingdom	Sanofi-Aventis Investigational Site Number 826007	London
United Kingdom	Sanofi-Aventis Investigational Site Number 826008	London
United Kingdom	Sanofi-Aventis Investigational Site Number 826011	London
United Kingdom	Sanofi-Aventis Investigational Site Number 826002	Manchester
United Kingdom	Sanofi-Aventis Investigational Site Number 826003	Northwood
United Kingdom	Sanofi-Aventis Investigational Site Number 826005	Sutton
United States	Sanofi-Aventis Investigational Site Number 840036	Albany	New York
United States	Sanofi-Aventis Investigational Site Number 840044	Albuquerque	New Mexico
United States	Sanofi-Aventis Investigational Site Number 840080	Anaheim	California
United States	Sanofi-Aventis Investigational Site Number 840043	Baton Rouge	Louisiana
United States	Sanofi-Aventis Investigational Site Number 840118	Bethlehem	Pennsylvania
United States	Sanofi-Aventis Investigational Site Number 840119	Birmingham	Alabama
United States	Sanofi-Aventis Investigational Site Number 840089	Boynton Beach	Florida
United States	Sanofi-Aventis Investigational Site Number 840035	Burlington	North Carolina
United States	Sanofi-Aventis Investigational Site Number 840085	Charleston	South Carolina
United States	Sanofi-Aventis Investigational Site Number 840024	Charlotte	North Carolina
United States	Sanofi-Aventis Investigational Site Number 840026	Charlotte	North Carolina
United States	Sanofi-Aventis Investigational Site Number 840087	Chicago	Illinois
United States	Sanofi-Aventis Investigational Site Number 840098	Cincinnati	Ohio
United States	Sanofi-Aventis Investigational Site Number 840078	Corpus Christi	Texas
United States	Sanofi-Aventis Investigational Site Number 840019	Decatur	Illinois
United States	Sanofi-Aventis Investigational Site Number 840115	Elk Grove Village	Illinois
United States	Sanofi-Aventis Investigational Site Number 840076	Fountain Valley	California
United States	Sanofi-Aventis Investigational Site Number 840120	Fountain Valley	California
United States	Sanofi-Aventis Investigational Site Number 840031	Gainesville	Florida
United States	Sanofi-Aventis Investigational Site Number 840041	Gainesville	Florida
United States	Sanofi-Aventis Investigational Site Number 840005	Goldsboro	North Carolina
United States	Sanofi-Aventis Investigational Site Number 840073	Greenbrae	California
United States	Sanofi-Aventis Investigational Site Number 840101	Hayward	California
United States	Sanofi-Aventis Investigational Site Number 840004	Hendersonville	North Carolina
United States	Sanofi-Aventis Investigational Site Number 840093	Hot Springs	Arizona
United States	Sanofi-Aventis Investigational Site Number 840047	Indianapolis	Indiana
United States	Sanofi-Aventis Investigational Site Number 840072	Indianapolis	Indiana
United States	Sanofi-Aventis Investigational Site Number 840081	Kansas City	Missouri
United States	Sanofi-Aventis Investigational Site Number 840011	Kettering	Ohio
United States	Sanofi-Aventis Investigational Site Number 840046	La Jolla	California
United States	Sanofi-Aventis Investigational Site Number 840094	Lake Success	New York
United States	Sanofi-Aventis Investigational Site Number 840049	Las Vegas	Nevada
United States	Sanofi-Aventis Investigational Site Number 840116	Loma Linda	California
United States	Sanofi-Aventis Investigational Site Number 840048	Long Beach	California
United States	Sanofi-Aventis Investigational Site Number 840088	Louisville	Kentucky
United States	Sanofi-Aventis Investigational Site Number 840002	Marshfield	Wisconsin
United States	Sanofi-Aventis Investigational Site Number 840084	Metairie	Louisiana
United States	Sanofi-Aventis Investigational Site Number 840122	Miami	Florida
United States	Sanofi-Aventis Investigational Site Number 840086	Middletown	Ohio
United States	Sanofi-Aventis Investigational Site Number 840034	Munster	Indiana
United States	Sanofi-Aventis Investigational Site Number 840074	Muscle Shoals	Alabama
United States	Sanofi-Aventis Investigational Site Number 840010	Naperville	Illinois
United States	Sanofi-Aventis Investigational Site Number 840015	New Orleans	Louisiana
United States	Sanofi-Aventis Investigational Site Number 840014	Newark	Delaware
United States	Sanofi-Aventis Investigational Site Number 840201	Oakland	California
United States	Sanofi-Aventis Investigational Site Number 840096	Paducah	Kentucky
United States	Sanofi-Aventis Investigational Site Number 840082	Pawtucket	Rhode Island
United States	Sanofi-Aventis Investigational Site Number 840033	Philadelphia	Pennsylvania
United States	Sanofi-Aventis Investigational Site Number 840012	Pittsburgh	Pennsylvania
United States	Sanofi-Aventis Investigational Site Number 840053	Pontiac	Michigan
United States	Sanofi-Aventis Investigational Site Number 840039	Portland	Oregon
United States	Sanofi-Aventis Investigational Site Number 840113	Quincy	Illinois
United States	Sanofi-Aventis Investigational Site Number 840070	Rockville	Maryland
United States	Sanofi-Aventis Investigational Site Number 840901	Roseville	California
United States	Sanofi-Aventis Investigational Site Number 840042	Sacramento	California
United States	Sanofi-Aventis Investigational Site Number 840301	Sacramento	California
United States	Sanofi-Aventis Investigational Site Number 840112	Salinas	California
United States	Sanofi-Aventis Investigational Site Number 840029	Salisbury	Maryland
United States	Sanofi-Aventis Investigational Site Number 840006	San Diego	California
United States	Sanofi-Aventis Investigational Site Number 840106	San Diego	California
United States	Sanofi-Aventis Investigational Site Number 840206	San Diego	California
United States	Sanofi-Aventis Investigational Site Number 840306	San Diego	California
United States	Sanofi-Aventis Investigational Site Number 840406	San Diego	California
United States	Sanofi-Aventis Investigational Site Number 840506	San Diego	California
United States	Sanofi-Aventis Investigational Site Number 840606	San Diego	California
United States	Sanofi-Aventis Investigational Site Number 840706	San Diego	California
United States	Sanofi-Aventis Investigational Site Number 840806	San Diego	California
United States	Sanofi-Aventis Investigational Site Number 840906	San Diego	California
United States	Sanofi-Aventis Investigational Site Number 840401	San Francisco	California
United States	Sanofi-Aventis Investigational Site Number 840601	San Jose	California
United States	Sanofi-Aventis Investigational Site Number 840501	Santa Clara	California
United States	Sanofi-Aventis Investigational Site Number 840099	Seattle	Washington
United States	Sanofi-Aventis Investigational Site Number 840801	South San Francisco	California
United States	Sanofi-Aventis Investigational Site Number 840037	Spartanburg	South Carolina
United States	Sanofi-Aventis Investigational Site Number 840052	St Louis	Missouri
United States	Sanofi-Aventis Investigational Site Number 840021	St Louis Park	Minnesota
United States	Sanofi-Aventis Investigational Site Number 840114	St. Louis	Missouri
United States	Sanofi-Aventis Investigational Site Number 840071	Stamford	Connecticut
United States	Sanofi-Aventis Investigational Site Number 840017	Syracuse	New York
United States	Sanofi-Aventis Investigational Site Number 840097	Syracuse	New York
United States	Sanofi-Aventis Investigational Site Number 840117	Temple	Texas
United States	Sanofi-Aventis Investigational Site Number 840079	The Villages	Florida
United States	Sanofi-Aventis Investigational Site Number 840008	Toledo	Ohio
United States	Sanofi-Aventis Investigational Site Number 840001	Vallejo	California
United States	Sanofi-Aventis Investigational Site Number 840701	Walnut Creek	California
United States	Sanofi-Aventis Investigational Site Number 840075	Winston-Salem	North Carolina
United States	Sanofi-Aventis Investigational Site Number 840095	Woonsocket	Rhode Island

Sponsors (3)

Lead Sponsor	Collaborator
Sanofi	NSABP Foundation Inc, Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Chile,  Czech Republic,  Denmark,  Estonia,  France,  Germany,  Greece,  Italy,  Korea, Republic of,  Netherlands,  New Zealand,  Norway,  Poland,  Puerto Rico,  Romania,  Russian Federation,  South Africa,  Spain,  Sweden,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From the date of the first randomization until the study data cut-off date, 07 February 2011 (approximately three years)	No
Secondary	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.	From the date of the first randomization until the occurrence of 561 OS events, 06 May 2010 (approximately 30 months)	No
Secondary	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.	From the date of the first randomization until the study data cut-off date, 06 May 2010 (approximately 30 months)	No
Secondary	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.	From the date of the first randomization up to 30 days after the treatment discontinuation or until TEAE was resolved or stabilized	Yes
Secondary	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.	Baseline, every other treatment cycle, 30 days and 90 days after the last infusion of aflibercept/placebo	No