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 (VELOUR)

This study has been completed.

Sponsor:

Collaborators:

Regeneron Pharmaceuticals

National Surgical Adjuvant Breast and Bowel Project (NSABP)

Information provided by (Responsible Party):

Sanofi

ClinicalTrials.gov Identifier:

NCT00561470

First received: November 20, 2007

Last updated: September 27, 2012

Last verified: March 2012

History of Changes

Results First Received: August 17, 2012

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver, Investigator); Primary Purpose: Treatment
Conditions:	Colorectal Neoplasms Neoplasm Metastasis
Interventions:	Drug: Placebo Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) Drug: FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Between 19 November 2007 and 16 March 2010, 614 participants were randomized to the placebo arm and 612 participants were randomized to the aflibercept arm.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Placebo/FOLFIRI	Participants with Metastatic Colorectal Cancer administered Placebo followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) every two weeks
Aflibercept/FOLFIRI	Participants with Metastatic Colorectal Cancer administered 4 mg/kg of Aflibercept, followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) every two weeks

Participant Flow: Overall Study

	Placebo/FOLFIRI	Aflibercept/FOLFIRI
STARTED	614	612
TREATED	609	607
SAFETY POPULATION	605 ^[1]	611 ^[2]
ONGOING TREATMENT	11 ^[3]	14 ^[3]
COMPLETED	0 ^[4]	0 ^[4]
NOT COMPLETED	614	612
Adverse Event	74	163
Disease progression	437	305
poor compliance to protocol	4	4
Lost to Follow-up	2	0
Physician Decision	21	20
Consent Withdrawn	2	6
Subject request	43	77
Metastatic surgery	10	12
Unauthorized procedure	3	1
Randomized but not treated	5	5
Missed visit window	1	4
Planning surgery	1	1
Ongoing Treatment	11	14

[1]	Treated participants excluding 4 who received at least 1 dose of Aflibercept
[2]	Treated participants including 4 from Placebo/FOLFIRI who received at least 1 dose of Aflibercept
[3]	Participants continuing treatment on the cutoff date of the final analysis
[4]	Participants met treatment discontinuation criteria or were ongoing treatment on the cutoff date

Baseline Characteristics

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Reporting Groups

	Description
Placebo/Folfiri	Participants with Metastatic Colorectal Cancer administered Placebo and FOLFIRI (Irinotecan, 5- Fluorouracil, and Leucovorin)
Aflibercept/Folfiri	Participants with Metastatic Colorectal Cancer administered 4 mg/kg of Aflibercept and FOLFIRI (Irinotecan, 5- Fluorouracil, and Leucovorin)
Total	Total of all reporting groups

Baseline Measures

	Placebo/Folfiri	Aflibercept/Folfiri	Total
Number of Participants [units: participants]	614	612	1226
Age [units: years] Mean ± Standard Deviation	60.2 ± 10.8	59.5 ± 10.5	59.8 ± 10.7
Age, Customized [units: participants]
<65 years	376	407	783
>=65 but <75 years	199	172	371
>=75 years	39	33	72
Gender, Customized [units: participants]
Male	353	365	718
Female	261	247	508
Race/Ethnicity, Customized [units: participants]
Caucasian/White	523	548	1071
Black	27	16	43
Asian/Oriental	51	35	86
Other	13	13	26
Region of Enrollment [units: participants]
ARGENTINA	4	2	6
AUSTRALIA	42	54	96
AUSTRIA	3	4	7
BELGIUM	37	45	82
BRAZIL	21	27	48
CHILE	31	33	64
CZECH REPUBLIC	30	47	77
DENMARK	9	6	15
ESTONIA	7	3	10
FRANCE	1	1	2
GERMANY	23	12	35
GREECE	9	10	19
ITALY	26	23	49
KOREA, REPUBLIC OF	39	26	65
NETHERLANDS	20	14	34
NEW ZEALAND	13	7	20
NORWAY	14	19	33
POLAND	24	32	56
PUERTO RICO	4	2	6
ROMANIA	16	16	32
RUSSIAN FEDERATION	35	40	75
SOUTH AFRICA	36	31	67
SPAIN	27	28	55
SWEDEN	10	4	14
TURKEY	4	2	6
UKRAINE	11	11	22
UNITED KINGDOM	47	52	99
UNITED STATES	71	61	132
Eastern Cooperative Oncology Group (ECOG) performance status score ^[1] [units: participants]
Participants with ECOG Score = 0	350	349	699
Participants with ECOG Score = 1	250	250	500
Participants with ECOG Score = 2	14	13	27
Prior Bevacizumab ^[2] [units: participants]
Yes	187	186	373
No	427	426	853

[1]	The ECOG score assesses how the disease affects a participant's daily living abilities. It ranges from 0-5, with 0 being the best and 5 being the worst outcome. "0" reflects a fully active participant, able to carry on all pre-disease performance without restriction. "1" reflects a participant restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. "2" reflects an ambulatory participant, who is up and about more than 50% of waking hours, and capable of all self-care but unable to carry out any work activities.
[2]	Number of participants randomized in the prior bevacizumab stratum as per the interactive voice response system (IVRS).

[1]

The ECOG score assesses how the disease affects a participant's daily living abilities. It ranges from 0-5, with 0 being the best and 5 being the worst outcome. "0" reflects a fully active participant, able to carry on all pre-disease performance without restriction. "1" reflects a participant restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. "2" reflects an ambulatory participant, who is up and about more than 50% of waking hours, and capable of all self-care but unable to carry out any work activities.

[2]

Number of participants randomized in the prior bevacizumab stratum as per the interactive voice response system (IVRS).

Outcome Measures

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1. Primary:

Overall Survival (OS) [ Time Frame: From the date of the first randomization until the study data cut-off date, 07 February 2011 (approximately three years) ]

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2. Secondary:

Progression-free Survival (PFS) Assessed by Independent Review Committee (IRC) [ Time Frame: From the date of the first randomization until the occurrence of 561 OS events, 06 May 2010 (approximately 30 months) ]

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3. 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 [ Time Frame: From the date of the first randomization until the study data cut-off date, 06 May 2010 (approximately 30 months) ]

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4. Secondary:

Number of Participants With Adverse Events (AE) [ Time Frame: From the date of the first randomization up to 30 days after the treatment discontinuation or until TEAE was resolved or stabilized ]

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5. 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 [ Time Frame: Baseline, every other treatment cycle, 30 days and 90 days after the last infusion of aflibercept/placebo ]

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Measure Type	Secondary
Measure Title	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
Measure Description	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.
Time Frame	Baseline, every other treatment cycle, 30 days and 90 days after the last infusion of aflibercept/placebo
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Immunogenicity population included all participants who were treated and tested for immunogenicity at least once post-baseline.

Reporting Groups

	Description
Placebo/FOLFIRI	Participants with Metastatic Colorectal Cancer administered Placebo and FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)
Aflibercept/FOLFIRI	Participants with Metastatic Colorectal Cancer administered Aflibercept and FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)

Measured Values

	Placebo/FOLFIRI	Aflibercept/FOLFIRI
Number of Participants Analyzed [units: participants]	526	521
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 [units: participants]
At least one positive sample in the ADA assay	18	8
At least one positive sample in the NAb assay	2	1

No statistical analysis provided for 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

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The investigator shall have the right to independently publish study results from his site after a multicenter publication, or 12 months after the completion of the study by all sites. He must provide the sponsor a copy of any such publication derived from the study for review and comment at least 45 days (20 days for abstracts) in advance of any submission, and delay publication till the approval of the publication is given in writing by the Sponsor (not to exceed ninety days).

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: International Clinical Development Study Director
Organization: sanofi-aventis
e-mail: contact-us@sanofi.com

No publications provided

Responsible Party:	Sanofi
ClinicalTrials.gov Identifier:	NCT00561470 History of Changes
Other Study ID Numbers:	EFC10262, EudraCT 2007-000820-42
Study First Received:	November 20, 2007
Results First Received:	August 17, 2012
Last Updated:	September 27, 2012
Health Authority:	United States: Food and Drug Administration Spain: Spanish Agency of Medicines Australia: Department of Health and Ageing Therapeutic Goods Administration

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