Safety and Quality of Life Study of Aflibercept in Patients With Metastatic Colorectal Cancer Previously Treated With an Oxaliplatin-Based Regimen

NCT ID: NCT01571284

Last Updated: 2018-04-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 781 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-30
• Study Completion Date: 2017-01-31

Brief Summary

Primary Objective:

To provide metastatic colorectal cancer participants with access to aflibercept and to document the overall safety in these participants

Secondary Objective:

To document the Health-Related Quality of Life of aflibercept in this participants population

Detailed Description

Each participants will be treated until disease progression, unacceptable toxicity, death, Investigator's decision or participant's refusal for further treatment (whichever comes first). Participants were followed-up during study treatment and for at least 30 days after last administration.

Conditions

Colorectal Cancer Metastatic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)

Aflibercept 4 mg/kg IV infusion over 60 minutes followed by Irinotecan 180 mg/m\^2 IV infusion over 90 minutes and Leucovorin 400 mg/m\^2 IV infusion over 120 minutes at the same time followed by 5-Fluorouracil (5-FU) 400 mg/m\^2 IV bolus over 2-4 minutes followed by 5-FU 2400 mg/m\^2 continuous IV infusion over 46 hours on Day 1 of each cycle (1 Cycle = 2 weeks), until disease progression (DP), unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.

Group Type: EXPERIMENTAL

AFLIBERCEPT AVE0005

Intervention Type: DRUG

Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous

FOLFIRI

Intervention Type: DRUG

irinotecan, 5-FU and leucovorin

Interventions

AFLIBERCEPT AVE0005

Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous

Intervention Type: DRUG

FOLFIRI

irinotecan, 5-FU and leucovorin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically proven adenocarcinoma of the colon or rectum.
• Metastatic disease.
• Eastern Cooperative Oncology Group performance status 0-1.
• One and only one prior chemotherapeutic regimen for metastatic disease. This prior chemotherapy was an oxaliplatin containing regimen. Participants must had progressed during or after the oxaliplatin based chemotherapy. Participants relapsed within 6 months of completion of oxaliplatin adjuvant chemotherapy were eligible.
• Signed written informed consent obtained prior to inclusion.

Exclusion Criteria

• Prior therapy with irinotecan.
• Inadequate bone marrow, liver and renal function: neutrophils < 1.5x109/L, platelets < 100x109/L, hemoglobin < 9.0 g/dL, total bilirubin >1.5 x upper normal limit (ULN), transaminases >3 x ULN (unless liver metastasis are present), alkaline phosphatase >3 x ULN (unless liver metastasis are present), serum creatinine > 1.5 x ULN.
• Less than 4 weeks from prior radiotherapy, prior chemotherapy, prior major surgery (or until the surgical wound were fully healed).
• Treatment with any investigational drug within the prior 30 days.
• Treatment with concomitant anticonvulsivant agents that were CYP3A4 inducers (phenytoin, phenobarbital, carbamazepine), unless discontinued >7 days.
• History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease.
• Prior malignancy (other than colorectal) including prior malignancy from which the participants had been disease free for < 5 years (except adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix).
• Any of the following within 6 months prior to study inclusion: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, severe congestive heart failure, stroke or transient ischemic attack.
• Any of the following within 3 months prior study inclusion: severe gastrointestinal bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive oesophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other uncontrolled thromboembolic event.
• Occurrence of deep vein thrombosis within 4 weeks, prior to study inclusion.
• Known acquired immunodeficiency syndrome (AIDS-related illnesses) or known HIV disease requiring antiretroviral treatment.
• Known dihydropyrimidine dehydrogenase deficiency.
• Predisposing colonic or small bowel disorders in which the symptoms were uncontrolled.
• Prior history of chronic enteropathy, inflammatory enteropathy, chronic diarrhea, unresolved bowel obstruction/sub-obstruction, more than hemicolectomy, extensive small intestine resection with chronic diarrhea.
• Known Gilbert's syndrome.
• Unresolved or unstable toxicity from any prior anti cancer therapy at the time of inclusion.
• History of anaphylaxis or known intolerance to atropine sulphate or loperamide or appropriate antiemetics to be administered in conjunction with FOLFIRI (irinotecan, 5-Fluorouracil, leucovorin).
• Severe acute or chronic medical condition, which could impair the ability of the participants to participate to the study.
• Urine protein-creatinine ratio (UPCR) >1 on morning spot urinalysis or proteinuria > 500 mg/24-h.
• Uncontrolled hypertension within 3 months prior to study inclusion.
• Participants on anticoagulant therapy with unstable dose of warfarin and/or had an out-of-therapeutic range INR within the 4 weeks prior to study inclusion.
• Evidence of clinically significant bleeding predisposition or underlying coagulopathy, non-healing wound.
• Pregnant or breast-feeding women.
• Participants with reproductive potential who were not agree to use an accepted effective method of contraception.

The above information wass not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 840-002

Muscle Shoals, Alabama, United States

Investigational Site Number 840-008

Corona, California, United States

Investigational Site Number 840-007

Fountain Valley, California, United States

Investigational Site Number 840-004

Riverside, California, United States

Investigational Site Number 840-006

Indianapolis, Indiana, United States

Investigational Site Number 840-011

Metairie, Louisiana, United States

Investigational Site Number 840-001

Rockville, Maryland, United States

Investigational Site Number 840-010

Howell Township, New Jersey, United States

Investigational Site Number 840-012

Albuquerque, New Mexico, United States

Investigational Site Number 840-009

Farmington, New Mexico, United States

Investigational Site Number 840-003

Lake Success, New York, United States

Investigational Site Number 840-005

Middletown, Ohio, United States

Investigational Site Number 056010

Aalst, , Belgium

Investigational Site Number 056015

Arlon, , Belgium

Investigational Site Number 056004

Bonheiden, , Belgium

Investigational Site Number 056001

Edegem, , Belgium

Investigational Site Number 056012

Ghent, , Belgium

Investigational Site Number 056009

Haine-Saint-Paul, , Belgium

Investigational Site Number 056003

Liège, , Belgium

Investigational Site Number 056007

Liège, , Belgium

Investigational Site Number 056014

Loverval, , Belgium

Investigational Site Number 056013

Turnhout, , Belgium

Investigational Site Number 056002

Verviers, , Belgium

Investigational Site Number 056011

Yvoir, , Belgium

Investigational Site Number 008

Brasília, , Brazil

Investigational Site Number 009

Curitiba, , Brazil

Investigational Site Number 012

Fortaleza, , Brazil

Investigational Site Number 006

Passo Fundo, , Brazil

Investigational Site Number 003

Porto Alegre, , Brazil

Investigational Site Number 002

Rio de Janeiro, , Brazil

Investigational Site Number 011

Salvador, , Brazil

Investigational Site Number 013

São José do Rio Preto, , Brazil

Investigational Site Number 001

São Paulo, , Brazil

Investigational Site Number 004

São Paulo, , Brazil

Investigational Site Number 005

São Paulo, , Brazil

Investigational Site Number 124002

Calgary, , Canada

Investigational Site Number 124003

Montreal, , Canada

Investigational Site Number 124005

Montreal, , Canada

Investigational Site Number 124004

Ottawa, , Canada

Investigational Site Number 124006

Québec, , Canada

Investigational Site Number 124001

Toronto, , Canada

Investigational Site Number 152001

Santiago, , Chile

Investigational Site Number 152003

Santiago, , Chile

Investigational Site Number 203005

Brno, , Czechia

Investigational Site Number 203003

Olomouc, , Czechia

Investigational Site Number 203001

Ostrava, , Czechia

Investigational Site Number 203002

Prague, , Czechia

Investigational Site Number 203004

Prague, , Czechia

Investigational Site Number 203006

Zlín, , Czechia

Investigational Site Number 208001

Cph Ø, , Denmark

Investigational Site Number 208003

Hillerød, , Denmark

Investigational Site Number 208002

Odense C, , Denmark

Investigational Site Number 246001

Oulu, , Finland

Investigational Site Number 246002

Turku, , Finland

Investigational Site Number 276-016

Aschaffenburg, , Germany

Investigational Site Number 276-010

Augsburg, , Germany

Investigational Site Number 276-011

Berlin, , Germany

Investigational Site Number 276-012

Erlangen, , Germany

Investigational Site Number 276-009

Frankfurt am Main, , Germany

Investigational Site Number 276-013

Frankfurt am Main, , Germany

Investigational Site Number 276-004

Halle, , Germany

Investigational Site Number 276-007

Krefeld, , Germany

Investigational Site Number 276-003

Lebach, , Germany

Investigational Site Number 276-019

Leipzig, , Germany

Investigational Site Number 276-008

Ludwigsburg, , Germany

Investigational Site Number 276-018

Magdeburg, , Germany

Investigational Site Number 276-014

Magdeburg, , Germany

Investigational Site Number 276-006

Moers, , Germany

Investigational Site Number 276-001

München, , Germany

Investigational Site Number 276-002

München, , Germany

Investigational Site Number 276-015

Northeim, , Germany

Investigational Site Number 276-017

Velbert, , Germany

Investigational Site Number 276-005

Weiden/Oberpfalz, , Germany

Investigational Site Number 276-020

Wolfsburg, , Germany

Investigational Site Number 372002

Dublin, , Ireland

Investigational Site Number 372004

Galway, , Ireland

Investigational Site Number 372001

Wilton, , Ireland

Investigational Site Number 376002

Haifa, , Israel

Investigational Site Number 376001

Jerusalem, , Israel

Investigational Site Number 376005

Petah Tikva, , Israel

Investigational Site Number 376003

Tel Aviv, , Israel

Investigational Site Number 376004

Tel Litwinsky, , Israel

Investigational Site Number 380-005

Ancona, , Italy

Investigational Site Number 380-029

Bergamo, , Italy

Investigational Site Number 380-021

Bologna, , Italy

Investigational Site Number 380-004

Brescia, , Italy

Investigational Site Number 380-007

Candiolo, , Italy

Investigational Site Number 380-012

Catania, , Italy

Investigational Site Number 380-019

Catanzaro, , Italy

Investigational Site Number 380-023

Florence, , Italy

Investigational Site Number 380-001

Genova, , Italy

Investigational Site Number 380-014

Meldola, , Italy

Investigational Site Number 380-016

Messina, , Italy

Investigational Site Number 380-013

Milan, , Italy

Investigational Site Number 380-015

Milan, , Italy

Investigational Site Number 380-025

Milan, , Italy

Investigational Site Number 380-022

Napoli, , Italy

Investigational Site Number 380-028

Novara, , Italy

Investigational Site Number 380-017

Padua, , Italy

Investigational Site Number 380-002

Pisa, , Italy

Investigational Site Number 380-008

Reggio Emilia, , Italy

Investigational Site Number 380-024

Roma, , Italy

Investigational Site Number 380-010

Roma, , Italy

Investigational Site Number 380-011

Roma, , Italy

Investigational Site Number 380-006

San Giovanni Rotondo, , Italy

Investigational Site Number 380-026

Sassari, , Italy

Investigational Site Number 380-020

Terni, , Italy

Investigational Site Number 380-009

Torino, , Italy

Investigational Site Number 380-003

Udine, , Italy

Investigational Site Number 380-018

Verona, , Italy

Investigational Site Number 1

Beirut, , Lebanon

Investigational Site Number 484002

Mexico City, , Mexico

Investigational Site Number 484009

Mexico City, , Mexico

Investigational Site Number 484010

México, D.F., , Mexico

Investigational Site Number 484001

Monterrey, , Mexico

Investigational Site Number 528001

Hoofddorp, , Netherlands

Investigational Site Number 528002

Zwolle, , Netherlands

Investigational Site Number 578002

Bergen, , Norway

Investigational Site Number 578001

Oslo, , Norway

Investigational Site Number 630-001

Rio Peidras, , Puerto Rico

Investigational Site Number 643003

Kazan', , Russia

Investigational Site Number 643001

Moscow, , Russia

Investigational Site Number 643004

Moscow, , Russia

Investigational Site Number 643005

Moscow, , Russia

Investigational Site Number 643002

Moscow, , Russia

Investigational Site Number 643006

Moscow, , Russia

Investigational Site Number 643009

Saint Petersburg, , Russia

Investigational Site Number 724016

Alicante, , Spain

Investigational Site Number 724008

Barakaldo, , Spain

Investigational Site Number 724012

Cáceres, , Spain

Investigational Site Number 724002

Córdoba, , Spain

Investigational Site Number 724013

Donostia / San Sebastian, , Spain

Investigational Site Number 724014

L'Hospitalet de Llobregat, , Spain

Investigational Site Number 724003

Madrid, , Spain

Investigational Site Number 724015

Madrid, , Spain

Investigational Site Number 724005

Madrid, , Spain

Investigational Site Number 724004

Málaga, , Spain

Investigational Site Number 724010

Sabadell, , Spain

Investigational Site Number 724011

Santander, , Spain

Investigational Site Number 724006

Santiago de Compostela, , Spain

Investigational Site Number 724001

Valencia, , Spain

Investigational Site Number 724009

Valencia, , Spain

Investigational Site Number 724007

Zaragoza, , Spain

Investigational Site Number 752_002

Jönköping, , Sweden

Investigational Site Number 752_001

Vaxjo, , Sweden

Investigational Site Number 764002

Bangkok, , Thailand

Investigational Site Number 764003

Bangkok, , Thailand

Investigational Site Number 764008

Bangkok, , Thailand

Investigational Site Number 764001

Bangkok, , Thailand

Investigational Site Number 764006

Bangkok, , Thailand

Investigational Site Number 764005

Bangkok,TH, , Thailand

Investigational Site Number 764009

Chiang Mai, , Thailand

Investigational Site Number 764004

Khon Kaen, , Thailand

Investigational Site Number 764010

Laksi, , Thailand

Investigational Site Number 764007

Lopburi, , Thailand

Investigational Site Number 792-06

Adana, , Turkey (Türkiye)

Investigational Site Number 792-01

Ankara, , Turkey (Türkiye)

Investigational Site Number 792-09

Ankara, , Turkey (Türkiye)

Investigational Site Number 792-08

Ankara, , Turkey (Türkiye)

Investigational Site Number 792-02

Çapa, , Turkey (Türkiye)

Investigational Site Number 792010

Edirne, , Turkey (Türkiye)

Investigational Site Number 792-05

Gaziantep, , Turkey (Türkiye)

Investigational Site Number 792012

Istanbul, , Turkey (Türkiye)

Investigational Site Number 792-03

Istanbul, , Turkey (Türkiye)

Investigational Site Number 792-04

Istanbul, , Turkey (Türkiye)

Investigational Site Number 792-007

Izmir, , Turkey (Türkiye)

Investigational Site Number 792011

Izmir, , Turkey (Türkiye)

Investigational Site Number 826005

Dudley, , United Kingdom

Investigational Site Number 826011

Hull, , United Kingdom

Investigational Site Number 826008

Leicester, , United Kingdom

Investigational Site Number 826007

London, , United Kingdom

Investigational Site Number 826012

London, , United Kingdom

Investigational Site Number 826003

Maidstone, , United Kingdom

Investigational Site Number 826009

Manchester, , United Kingdom

Investigational Site Number 826004

Newcastle upon Tyne, , United Kingdom

Investigational Site Number 826006

Northwood, , United Kingdom

Investigational Site Number 826002

Southampton, , United Kingdom

Investigational Site Number 826001

Sutton, , United Kingdom

Investigational Site Number 826010

Taunton, , United Kingdom

Countries

United States; Belgium; Brazil; Canada; Chile; Czechia; Denmark; Finland; Germany; Ireland; Israel; Italy; Lebanon; Mexico; Netherlands; Norway; Puerto Rico; Russia; Spain; Sweden; Thailand; Turkey (Türkiye); United Kingdom

References

Riechelmann RP, Srimuninnimit V, Bordonaro R, Kavan P, Di Bartolomeo M, Maiello E, Cicin I, Garcia-Alfonso P, Chau I, Fedyanin MY, Martos CF, Ter-Ovanesov M, Peeters M, Ko YJ, Yalcin S, Karthaus M, Aparicio J, Heinemann V, Picard P, Bury D, Drea E, Sobrero A. Aflibercept Plus FOLFIRI for Second-line Treatment of Metastatic Colorectal Cancer: Observations from the Global Aflibercept Safety and Health-Related Quality-of-Life Program (ASQoP). Clin Colorectal Cancer. 2019 Sep;18(3):183-191.e3. doi: 10.1016/j.clcc.2019.05.003. Epub 2019 May 15.

Reference Type: DERIVED

PMID: 31221542 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2011-005724-17

Identifier Type: -

Identifier Source: secondary_id

U1111-1125-8949

Identifier Type: OTHER

Identifier Source: secondary_id

AFLIBC06097

Identifier Type: -

Identifier Source: org_study_id