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

A Multicenter, Single Arm, Open Label Clinical Trial to Evaluate the Safety and Health-Related Quality of Life of Aflibercept in Patients With Metastatic Colorectal Cancer (mCRC) Previously Treated With an Oxaliplatin-Containing Regimen

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

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer Metastatic
• Intervention / Treatment: Drug: AFLIBERCEPT AVE0005; Drug: FOLFIRI

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.

• Study Type: Interventional
• Enrollment (Actual): 781
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium, 9300
    • Investigational Site Number 056010
  • Arlon, Belgium, 6700
    • Investigational Site Number 056015
  • Bonheiden, Belgium, 2820
    • Investigational Site Number 056004
  • Edegem, Belgium, 2650
    • Investigational Site Number 056001
  • Gent, Belgium, 9000
    • Investigational Site Number 056012
  • Haine-Saint-Paul, Belgium, 7100
    • Investigational Site Number 056009
  • Liège, Belgium, 4000
    • Investigational Site Number 056003
  • Liège, Belgium, 4000
    • Investigational Site Number 056007
  • Loverval, Belgium, 6280
    • Investigational Site Number 056014
  • Turnhout, Belgium, 2300
    • Investigational Site Number 056013
  • Verviers, Belgium, 4800
    • Investigational Site Number 056002
  • Yvoir, Belgium, 5530
    • Investigational Site Number 056011
• Brazil
  • Brasília, Brazil, 70390-150
    • Investigational Site Number 008
  • Curitiba, Brazil, 80530-010
    • Investigational Site Number 009
  • Fortaleza, Brazil
    • Investigational Site Number 012
  • Passo Fundo, Brazil, 99010-260
    • Investigational Site Number 006
  • Porto Alegre, Brazil, 90470-340
    • Investigational Site Number 003
  • Rio de Janeiro, Brazil, 22793-080
    • Investigational Site Number 002
  • Salvador, Brazil, 40170-070
    • Investigational Site Number 011
  • Sao Jose do Rio Preto, Brazil, 15090-000
    • Investigational Site Number 013
  • São Paulo, Brazil, 01246-000
    • Investigational Site Number 001
  • São Paulo, Brazil, 01308-050
    • Investigational Site Number 004
  • São Paulo, Brazil, 01321-000
    • Investigational Site Number 005
• Canada
  • Calgary, Canada, T2N 4N2
    • Investigational Site Number 124002
  • Montreal, Canada, H1T 2M4
    • Investigational Site Number 124003
  • Montreal, Canada, H2W1S6
    • Investigational Site Number 124005
  • Ottawa, Canada, K1H8L6
    • Investigational Site Number 124004
  • Québec, Canada, G1S4L8
    • Investigational Site Number 124006
  • Toronto, Canada, M4N3M5
    • Investigational Site Number 124001
• Chile
  • Santiago, Chile
    • Investigational Site Number 152001
  • Santiago, Chile
    • Investigational Site Number 152003
• Czechia
  • Brno, Czechia, 65653
    • Investigational Site Number 203005
  • Olomouc, Czechia, 77900
    • Investigational Site Number 203003
  • Ostrava, Czechia, 70852
    • Investigational Site Number 203001
  • Praha 2, Czechia, 12808
    • Investigational Site Number 203002
  • Praha 5, Czechia, 15006
    • Investigational Site Number 203004
  • Zlin, Czechia
    • Investigational Site Number 203006
• Denmark
  • Cph Ø, Denmark, 2100
    • Investigational Site Number 208001
  • Hillerød, Denmark, 3400
    • Investigational Site Number 208003
  • Odense C, Denmark, 5000
    • Investigational Site Number 208002
• Finland
  • Oulu, Finland, 90220
    • Investigational Site Number 246001
  • Turku, Finland, 20520
    • Investigational Site Number 246002
• Germany
  • Aschaffenburg, Germany, 63739
    • Investigational Site Number 276-016
  • Augsburg, Germany, 86150
    • Investigational Site Number 276-010
  • Berlin, Germany, 10707
    • Investigational Site Number 276-011
  • Erlangen, Germany, 91054
    • Investigational Site Number 276-012
  • Frankfurt am Main, Germany, 60389
    • Investigational Site Number 276-009
  • Frankfurt am Main, Germany, 60590
    • Investigational Site Number 276-013
  • Halle, Germany, 06120
    • Investigational Site Number 276-004
  • Krefeld, Germany, 47805
    • Investigational Site Number 276-007
  • Lebach, Germany, 66822
    • Investigational Site Number 276-003
  • Leipzig, Germany, 04103
    • Investigational Site Number 276-019
  • Ludwigsburg, Germany, 71640
    • Investigational Site Number 276-008
  • Magdeburg, Germany, 39104
    • Investigational Site Number 276-018
  • Magdeburg, Germany, 39130
    • Investigational Site Number 276-014
  • Moers, Germany, 47441
    • Investigational Site Number 276-006
  • München, Germany, 81377
    • Investigational Site Number 276-001
  • München, Germany, 81737
    • Investigational Site Number 276-002
  • Northeim, Germany, 37154
    • Investigational Site Number 276-015
  • Velbert, Germany, 42551
    • Investigational Site Number 276-017
  • Weiden/Oberpfalz, Germany, 92637
    • Investigational Site Number 276-005
  • Wolfsburg, Germany, 38440
    • Investigational Site Number 276-020
• Ireland
  • Dublin 24, Ireland
    • Investigational Site Number 372002
  • Galway, Ireland
    • Investigational Site Number 372004
  • Wilton, Ireland
    • Investigational Site Number 372001
• Israel
  • Haifa, Israel, 31096
    • Investigational Site Number 376002
  • Jerusalem, Israel, 91120
    • Investigational Site Number 376001
  • Petach Tikva, Israel, 49100
    • Investigational Site Number 376005
  • Tel Aviv, Israel, 64239
    • Investigational Site Number 376003
  • Tel Hashomer, Israel, 52621
    • Investigational Site Number 376004
• Italy
  • Ancona, Italy, 60100
    • Investigational Site Number 380-005
  • Bergamo, Italy, 24128
    • Investigational Site Number 380-029
  • Bologna, Italy, 40133
    • Investigational Site Number 380-021
  • Brescia, Italy
    • Investigational Site Number 380-004
  • Candiolo, Italy
    • Investigational Site Number 380-007
  • Catania, Italy
    • Investigational Site Number 380-012
  • Catanzaro, Italy
    • Investigational Site Number 380-019
  • Firenze, Italy
    • Investigational Site Number 380-023
  • Genova, Italy, 16132
    • Investigational Site Number 380-001
  • Meldola, Italy
    • Investigational Site Number 380-014
  • Messina, Italy
    • Investigational Site Number 380-016
  • Milano, Italy
    • Investigational Site Number 380-013
  • Milano, Italy
    • Investigational Site Number 380-015
  • Milano, Italy
    • Investigational Site Number 380-025
  • Napoli, Italy
    • Investigational Site Number 380-022
  • Novara, Italy
    • Investigational Site Number 380-028
  • Padova, Italy
    • Investigational Site Number 380-017
  • Pisa, Italy
    • Investigational Site Number 380-002
  • Reggio Emilia, Italy, 42125
    • Investigational Site Number 380-008
  • Roma, Italy, 00189
    • Investigational Site Number 380-024
  • Roma, Italy
    • Investigational Site Number 380-010
  • Roma, Italy
    • Investigational Site Number 380-011
  • San Giovanni Rotondo, Italy
    • Investigational Site Number 380-006
  • Sassari, Italy
    • Investigational Site Number 380-026
  • Terni, Italy
    • Investigational Site Number 380-020
  • Torino, Italy
    • Investigational Site Number 380-009
  • Udine, Italy
    • Investigational Site Number 380-003
  • Verona, Italy
    • Investigational Site Number 380-018
• Lebanon
  • Beirut, Lebanon
    • Investigational Site Number 1
• Mexico
  • Mexico DF, Mexico, 06760
    • Investigational Site Number 484002
  • Mexico DF, Mexico, 57205
    • Investigational Site Number 484009
  • Monterrey, Mexico, 64060
    • Investigational Site Number 484001
  • México, D.F., Mexico, 06726
    • Investigational Site Number 484010
• Netherlands
  • Hoofddorp, Netherlands, 2134TM
    • Investigational Site Number 528001
  • Zwolle, Netherlands, 8025AB
    • Investigational Site Number 528002
• Norway
  • Bergen, Norway, 5021
    • Investigational Site Number 578002
  • Oslo, Norway, 0407
    • Investigational Site Number 578001
• Puerto Rico
  • Rio Peidras, Puerto Rico, 927
    • Investigational Site Number 630-001
• Russian Federation
  • Kazan, Russian Federation, 420029
    • Investigational Site Number 643003
  • Moscow, Russian Federation, 115478
    • Investigational Site Number 643001
  • Moscow, Russian Federation, 115478
    • Investigational Site Number 643005
  • Moscow, Russian Federation, 115478
    • Investigational Site Number 643004
  • Moscow, Russian Federation, 123448
    • Investigational Site Number 643002
  • Moscow, Russian Federation, 129301
    • Investigational Site Number 643006
  • Saint-Petersburg, Russian Federation, 186646
    • Investigational Site Number 643009
• Spain
  • Alicante, Spain, 03010
    • Investigational Site Number 724016
  • Barakaldo, Spain, 48903
    • Investigational Site Number 724008
  • Cáceres, Spain, 10003
    • Investigational Site Number 724012
  • Córdoba, Spain, 14004
    • Investigational Site Number 724002
  • Donostia, Spain, 20014
    • Investigational Site Number 724013
  • L'Hospitalet de Llobregat, Spain, 08907
    • Investigational Site Number 724014
  • Madrid, Spain, 28007
    • Investigational Site Number 724003
  • Madrid, Spain, 28034
    • Investigational Site Number 724015
  • Madrid, Spain, 28041
    • Investigational Site Number 724005
  • Málaga, Spain, 29010
    • Investigational Site Number 724004
  • Sabadell, Spain, 08208
    • Investigational Site Number 724010
  • Santander, Spain, 39008
    • Investigational Site Number 724011
  • Santiago de Compostela, Spain, 15706
    • Investigational Site Number 724006
  • Valencia, Spain, 46009
    • Investigational Site Number 724001
  • Valencia, Spain, 46009
    • Investigational Site Number 724009
  • Zaragoza, Spain, 50009
    • Investigational Site Number 724007
• Sweden
  • Jönköping, Sweden, 55185
    • Investigational Site Number 752_002
  • Växjö, Sweden, 35185
    • Investigational Site Number 752_001
• Thailand
  • Bangkok, Thailand, 10330
    • Investigational Site Number 764002
  • Bangkok, Thailand, 10400
    • Investigational Site Number 764003
  • Bangkok, Thailand, 10400
    • Investigational Site Number 764008
  • Bangkok, Thailand
    • Investigational Site Number 764001
  • Bangkok, Thailand
    • Investigational Site Number 764006
  • Bangkok,TH, Thailand
    • Investigational Site Number 764005
  • Chiang Mai, Thailand, 50200
    • Investigational Site Number 764009
  • Khon Kaen, Thailand, 40002
    • Investigational Site Number 764004
  • Laksi, Thailand, 10210
    • Investigational Site Number 764010
  • Lopburi, Thailand, 15000
    • Investigational Site Number 764007
• Turkey
  • Adana, Turkey, 01250
    • Investigational Site Number 792-06
  • Ankara, Turkey, 06100
    • Investigational Site Number 792-01
  • Ankara, Turkey, 06200
    • Investigational Site Number 792-09
  • Ankara, Turkey
    • Investigational Site Number 792-08
  • Capa, Turkey, 34390
    • Investigational Site Number 792-02
  • Edirne, Turkey
    • Investigational Site Number 792010
  • Gaziantep, Turkey
    • Investigational Site Number 792-05
  • Istanbul, Turkey, 34093
    • Investigational Site Number 792012
  • Istanbul, Turkey, 34865
    • Investigational Site Number 792-03
  • Istanbul, Turkey
    • Investigational Site Number 792-04
  • Izmir, Turkey, 35100
    • Investigational Site Number 792-007
  • Izmir, Turkey
    • Investigational Site Number 792011
• United Kingdom
  • Dudley, United Kingdom, DY1 2HQ
    • Investigational Site Number 826005
  • Hull, United Kingdom, HU165JQ
    • Investigational Site Number 826011
  • Leicester, United Kingdom, LE15WW
    • Investigational Site Number 826008
  • London, United Kingdom, NW1 2PJ
    • Investigational Site Number 826007
  • London, United Kingdom, SE17EH
    • Investigational Site Number 826012
  • Maidstone,, United Kingdom, ME169QQ
    • Investigational Site Number 826003
  • Manchester, United Kingdom, M204BX
    • Investigational Site Number 826009
  • Newcastle upon tyne, United Kingdom, NE77DN
    • Investigational Site Number 826004
  • Northwood, United Kingdom, HA62RN
    • Investigational Site Number 826006
  • Southampton, United Kingdom, SO60YD
    • Investigational Site Number 826002
  • Sutton, United Kingdom, SM25PT
    • Investigational Site Number 826001
  • Taunton, United Kingdom, TA15DA
    • Investigational Site Number 826010
• United States
  • Alabama
    • Muscle Shoals, Alabama, United States, 35661
      • Investigational Site Number 840-002
  • California
    • Corona, California, United States, 92879
      • Investigational Site Number 840-008
    • Fountain Valley, California, United States, 92708
      • Investigational Site Number 840-007
    • Riverside, California, United States, 92501
      • Investigational Site Number 840-004
  • Indiana
    • Indianapolis, Indiana, United States, 46254
      • Investigational Site Number 840-006
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Investigational Site Number 840-011
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Investigational Site Number 840-001
  • New Jersey
    • Howell, New Jersey, United States, 07731
      • Investigational Site Number 840-010
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Investigational Site Number 840-012
    • Farmington, New Mexico, United States, 87401
      • Investigational Site Number 840-009
  • New York
    • Lake Success, New York, United States, 11042
      • Investigational Site Number 840-003
  • Ohio
    • Middletown, Ohio, United States, 45042
      • Investigational Site Number 840-005

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: AFLIBERCEPT AVE0005; Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous; Drug: FOLFIRI; irinotecan, 5-FU and leucovorin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an adverse event (AE) without regard to possibility of causal relationship with this treatment. A serious AE (SAE): Any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Version 4.03 was used to assess severity (Grade 1=mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening/disabling) of AEs.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Number of Participants With Abnormal Hematological Parameters	Abnormal hematological parameters included: anaemia, thrombocytopenia, leukopenia and neutropenia. Number of participants with each of these parameters were analyzed by grades (All Grades and Grades 3-4 as per NCI CTCAE (Version 4.03), where Grade 1=mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening/disabling. All Grades included Grades 1-4.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Number of Participants With International Normalized Ratio (INR)	The INR is a derived measure of the prothrombin time. The INR is the ratio of a participant's prothrombin time to a normal control sample. Normal range (without anti coagulation therapy): 0.8-1.2; Targeted range (with anti coagulation therapy) 2.0-3.0.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Number of Participants With Abnormal Electrolytes Parameters	Abnormal electrolytes parameters included: hyponatremia, hypernatremia, hypocalcemia, hypercalcemia, hypokalemia, and hyperkalemia. Number of participants with each of these parameters were analyzed by grades ( All Grades and Grades 3-4 as per NCI CTCAE Version 4.03, where Grade 1=mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening/disabling. All Grades included Grades 1-4.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Number of Participants With Abnormal Renal and Liver Function Parameters	Renal and liver function parameters included: creatinine, hyperbilirubinemia, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase. Number of participants with each of these parameters were analyzed by grades (All Grades and Grades 3-4) as per NCI CTCAE version 4.03, where Grade 1=mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening/disabling. All Grades included Grades 1-4.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Creatinine Clearance of Aflibercept Plus FOLFIRI	Creatinine clearance is a measure of kidney function. Creatinine clearance rate is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Creatinine clearance can be measured directly or estimated using established formulas. For this study, the creatinine clearance was calculated using the Cockroft-Gault or Modification of Diet in Renal Disease (MDRD).	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Number of Participants With Other Abnormal Biochemistry Parameters	Other abnormal biochemistry parameters included: hypoglycemia, hyperglycemia and hypoalbuminemia. Number of participants with each of these parameters were analyzed by grades (All Grades and Grades 3-4) as per NCI CTCAE Version 4.03, where Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening/disabling. All Grades included Grades 1-4.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Number of Participants With Abnormal Non-Gradable Biochemistry Parameters	Non-gradeable biochemistry parameters included; chloride, urea, total protein, blood urea nitrogen (BUN) and lactate dehydrogenase (LDH). Number of participants with <lower limit of normal ranges (LLN) and >upper limit of normal ranges (ULN) for each of these parameters were reported.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Number of Participants With Proteinuria Events	Proteinuria is defined as the ratio of protein to creatinine. Number of participants with proteinuria were analyzed by grades (Grades 1, 2, 3 ,4) as per NCI CTCAE Version 4.03 where Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening/disabling.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Number of Participants With Proteinuria Grade >=2	Proteinuria is defined as the ratio of protein to creatinine. Number of participants with proteinuria grade >=2 (graded as per NCI CTCAE Version 4.03), where Grade>=2 represents moderate to life-threatening/disabling event.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Number of Participants With Urinary Protein-Creatinine Ratio (UPCR)	Urinary protein creatinine ratio (UPCR) corresponds to the ratio of the urinary protein and urinary creatinine concentration (expressed in mg/dL). This ratio provides an accurate quantification of 24-hours urinary protein excretion. There is a high correlation between morning UPCR and 24-hour proteinuria in participants with normal or reduced renal functions. Normal ratio is < or = 1.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Number of Participants With Proteinuria (Grade>=2) Concomitant With Hematuria and /or Hypertension	Proteinuria is defined as the presence of excess proteins in the urine (assessed either by spot sample, dipstick/ urine protein or 24 hour urine collection). Hematuria is defined as the presence of blood in urine (positive dipstick for RBC or reported AE). Number of participants with proteinuria grade >=2 (graded as per NCI CTCAE Version 4.03), where Grade>=2 represents moderate to life-threatening/disabling event. Hypertension (high blood pressure) is defined as having a blood pressure reading of more than 140/90 mmHg over a number of weeks.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Number of Participants With Cycle Delay and/or Dose Modification	A theoretical cycle is a 2 week period i.e. 14 days. A cycle is delayed if duration of previous cycle is greater than 14+2 days ; dose modification includes dose reduction and dose omission.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment for Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30 Score): Global Health Status	EORTC-QLQ-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical,role,emotional,cognitive,social), 3 symptom scales (fatigue,nausea/vomiting,pain) & other single items. For each item,high score represented high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health & quality of life, coded on 7-point scale (1=very poor to 7=excellent).EORTC QLQ-C30 observed values and change from baseline for global health status (scoring of questions 29 & 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Answers were converted into grading scale, with values between 0 and 100. A high score represented a favourable outcome with a best quality of life for participant.	Pre-dose at Baseline, Day 1 of every odd cycle (from Cycle 3 to 35); at the end of treatment (EOT) (within 30 days of last treatment) (maximum exposure: 214 weeks)
Mean Change From Baseline in HRQL EORTC QLQ-C30 Score: Functional Scales	EORTC-QLQ-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical,role,emotional,cognitive,social), 3 symptom scales (fatigue,nausea/vomiting,pain) & other single items. For each item,high score represented high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health & quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 observed values and change from baseline for global health status (scoring of questions 29 & 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28).Answers were converted into grading scale, with values between 0 and 100. A high score represented a favourable outcome with a best quality of life for participant.	Pre-dose at Baseline, Day 1 of every odd cycle (from Cycle 3 to 35); at EOT (within 30 days of last treatment) (maximum exposure: 214 weeks)
Change From Baseline in HRQL EORTC QLQ-C30 Score: Symptom Scales	EORTC-QLQ-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical,role,emotional,cognitive,social), 3 symptom scales (fatigue,nausea/vomiting,pain) & other single items. For each item,high score represented high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health & quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 observed values and change from baseline for global health status (scoring of questions 29 & 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Answers were converted into grading scale, with values between 0 and 100. A high score represented a favorable outcome with a best quality of life for participant.	Pre-dose at Baseline, Day 1 of every odd cycle (from Cycle 3 to 35); at EOT (within 30 days of last treatment) (maximum exposure: 214 weeks)
Change From Baseline in HRQL EQ-5D-3L Quality of Life: Single Index Utility Score	EQ-5D was a standardized HRQL questionnaire consisting of EQ-5D descriptive system and Visual Analogue Scale (VAS). EQ-5D descriptive system comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression measured on 3 levels (no problem, some problems & severe problems) within a particular EQ-5D dimension. 5 dimensional 3-level system was converted into single index utility score. Possible values for single index utility score ranged from -0.594 (severe problems in all dimensions) to 1.0 (no problem in all dimensions) on scale where 1 represented best possible health state.	Pre-dose at Baseline, Day 1 of every odd cycle (from Cycle 3 to 35); at EOT (within 30 days of last treatment) (maximum exposure: 214 weeks)
Change From Baseline in HRQL EQ-5D-3L VAS Score	EQ-5D was a standardized HRQL questionnaire consisting of EQ-5D descriptive system and VAS. EQ-5D descriptive system comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression measured on 3 levels (no problem, some problems & severe problems) within a particular EQ-5D dimension. 5 dimensional 3-level system was converted into single index utility score. The VAS recorded the respondent's self-rated health on a vertical visual analogue scale. The VAS 'thermometer' has endpoints of 100 (Best imaginable health state) at the top and 0 (Worst imaginable health state) at the bottom. This information can be used as a quantitative measure of health outcome as judged by the individual respondents.	Pre-dose at Baseline, Day 1 of every odd cycle (from Cycle 3 to 35); at EOT (within 30 days of last treatment) (maximum exposure: 214 weeks)

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2012
• Primary Completion (Actual): January 31, 2017
• Study Completion (Actual): January 31, 2017

Study Registration Dates

• First Submitted: April 3, 2012
• First Submitted That Met QC Criteria: April 3, 2012
• First Posted (Estimate): April 5, 2012

Study Record Updates

• Last Update Posted (Actual): April 17, 2018
• Last Update Submitted That Met QC Criteria: March 19, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: AFLIBC06097; 2011-005724-17; U1111-1125-8949 (Other Identifier: UTN)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No