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Trial record 70 of 167 for:    colon cancer AND Colorectal Neoplasms | ( Map: New Jersey, United States )

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

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ClinicalTrials.gov Identifier: NCT01571284
Recruitment Status : Completed
First Posted : April 5, 2012
Results First Posted : February 27, 2018
Last Update Posted : April 17, 2018
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Colorectal Cancer Metastatic
Interventions Drug: AFLIBERCEPT AVE0005
Drug: FOLFIRI
Enrollment 781
Recruitment Details The study was conducted at 151 sites in 23 countries. A total of 798 participants were screened between 30 May 2012 and 03 January 2015, out of which 781 participants were enrolled and 779 participants were treated.
Pre-assignment Details Participants enrolled in the study to assess the safety of Aflibercept in participants treated with a combination of Aflibercept with FOLFIRI regimen (Irinotecan, Leucovorin and 5-Fluorouracil [5-FU]).
Arm/Group Title Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Hide Arm/Group Description Aflibercept 4 mg/kg intravenous (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-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.
Period Title: Overall Study
Started 781
Safety Population [1] 779
Completed 612 [2]
Not Completed 169
Reason Not Completed
Participant's decision             84
Lost to Follow-up             3
Enrolled but not treated             2
Other than specified above             80
[1]
Participants who signed informed consent form and received at least part of one dose of treatment.
[2]
403 participants with DP and 209 with adverse events were considered as completed.
Arm/Group Title Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Hide Arm/Group Description 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-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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Baseline Participants 779
Hide Baseline Analysis Population Description
Safety population defined as the participants who signed the informed consent form and received at least part of one dose of study treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 779 participants
60.3  (11.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 779 participants
Female
314
  40.3%
Male
465
  59.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
White Number Analyzed 779 participants
631
  81.0%
Black or African Number Analyzed 779 participants
8
   1.0%
American Asian Number Analyzed 779 participants
121
  15.5%
Other Number Analyzed 779 participants
19
   2.4%
Body Surface Area (BSA)  
Mean (Standard Deviation)
Unit of measure:  M^2
Number Analyzed 779 participants
1.80  (0.23)
Systolic Blood Pressure   [1] 
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 776 participants
126.4  (13.4)
[1]
Measure Analysis Population Description: Number of participants analyzed = participants with available data for specified measure.
Diastolic Blood Pressure   [1] 
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 776 participants
76.4  (9.0)
[1]
Measure Analysis Population Description: Number of participants analyzed = participants with available data for specified measure.
Any Relevant Medical/Surgical History   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 779 participants
640
  82.2%
[1]
Measure Description: Any relevant medical/surgical history including detailed cardiovascular risk factors and prior vascular events if any.
History of Thrombovascular Event and/or Presence of Cardiovascular Risk Factor  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 779 participants
424
  54.4%
Time From Initial Histological Diagnosis till Baseline Visit  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 779 participants
19.1  (17.2)
Location of Primary Tumor  
Measure Type: Count of Participants
Unit of measure:  Participants
Colon Number Analyzed 779 participants
406
  52.1%
Recto sigmoid Number Analyzed 779 participants
171
  22.0%
Rectum Number Analyzed 779 participants
200
  25.7%
Other Number Analyzed 779 participants
2
   0.3%
Histology  
Measure Type: Count of Participants
Unit of measure:  Participants
Adenocarcinoma Number Analyzed 779 participants
778
  99.9%
Other Number Analyzed 779 participants
1
   0.1%
Organs with Metastases at Baseline  
Measure Type: Count of Participants
Unit of measure:  Participants
1 Number Analyzed 779 participants
358
  46.0%
>1 Number Analyzed 779 participants
421
  54.0%
Eastern Cooperative Oncology Group Performance Status (ECOG PS)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
0 Number Analyzed 779 participants
484
  62.1%
1 Number Analyzed 779 participants
292
  37.5%
Missing Number Analyzed 779 participants
3
   0.4%
[1]
Measure Description: ECOG PS is used to assess how the disease affects the daily living abilities of the participant. It ranges on the scale from 0-5 (0= normal activity; 1= symptoms but ambulatory; 2= in bed for less than (<) 50 percent (%) of the time; 3= in bed for greater than (>) 50% of the time; 4= 100% bedridden; 5= dead.
1.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Hide Description 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.
Time Frame Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population defined as the participants who signed the informed consent form and received at least part of one dose of study treatment.
Arm/Group Title Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Hide Arm/Group Description:
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-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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed 779
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE (All Grades)
769
  98.7%
Any TEAEs (Grades 3-4)
609
  78.2%
Any serious TEAE
272
  34.9%
Any serious related TEAE
159
  20.4%
Any TEAE leading to death
47
   6.0%
Any TEAE (permanent treatment discontinuation)
208
  26.7%
Any TEAE (premature treatment discontinuation)
104
  13.4%
2.Primary Outcome
Title Number of Participants With Abnormal Hematological Parameters
Hide Description 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.
Time Frame Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Here, 'Number Analyzed = participants with available data for specified categories.
Arm/Group Title Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Hide Arm/Group Description:
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-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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed 779
Measure Type: Count of Participants
Unit of Measure: Participants
Anaemia: All Grades Number Analyzed 744 participants
535
  71.9%
Anaemia: Grades 3-4 Number Analyzed 744 participants
14
   1.9%
Thrombocytopenia: All Grades Number Analyzed 745 participants
293
  39.3%
Thrombocytopenia: Grades 3-4 Number Analyzed 745 participants
13
   1.7%
Leukopenia: All Grades Number Analyzed 745 participants
532
  71.4%
Leukopenia: Grades 3-4 Number Analyzed 745 participants
72
   9.7%
Neutropenia: All Grades Number Analyzed 744 participants
450
  60.5%
Neutropenia: Grades 3-4 Number Analyzed 744 participants
227
  30.5%
3.Primary Outcome
Title Number of Participants With International Normalized Ratio (INR)
Hide Description 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.
Time Frame Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Here, 'Number Analyzed' = participants with available data for specified categories.
Arm/Group Title Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Hide Arm/Group Description:
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-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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed 779
Measure Type: Count of Participants
Unit of Measure: Participants
INR<1.5 Number Analyzed 110 participants
106
  96.4%
INR>=1.5 to <3 Number Analyzed 110 participants
0
   0.0%
INR>=3 to <5 Number Analyzed 110 participants
2
   1.8%
INR>=5 Number Analyzed 110 participants
2
   1.8%
4.Primary Outcome
Title Number of Participants With Abnormal Electrolytes Parameters
Hide Description 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.
Time Frame Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Here, 'Number Analyzed' = participants with available data for specified categories.
Arm/Group Title Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Hide Arm/Group Description:
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-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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed 779
Measure Type: Count of Participants
Unit of Measure: Participants
Hyponatremia: All Grades Number Analyzed 736 participants
181
  24.6%
Hyponatremia: Grades 3-4 Number Analyzed 736 participants
32
   4.3%
Hypernatremia: All Grades Number Analyzed 736 participants
75
  10.2%
Hypernatremia: Grades 3-4 Number Analyzed 736 participants
1
   0.1%
Hypocalcemia: All Grades Number Analyzed 682 participants
213
  31.2%
Hypocalcemia: Grades 3-4 Number Analyzed 682 participants
5
   0.7%
Hypercalcemia: All Grades Number Analyzed 682 participants
52
   7.6%
Hypercalcemia: Grades 3-4 Number Analyzed 682 participants
2
   0.3%
Hypokalemia: All Grades Number Analyzed 734 participants
121
  16.5%
Hypokalemia: Grades 3-4 Number Analyzed 734 participants
16
   2.2%
Hyperkalemia: All Grades Number Analyzed 734 participants
166
  22.6%
Hyperkalemia: Grades 3-4 Number Analyzed 734 participants
10
   1.4%
5.Primary Outcome
Title Number of Participants With Abnormal Renal and Liver Function Parameters
Hide Description 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.
Time Frame Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Here, 'Number Analyzed' = participants with available data for specified categories.
Arm/Group Title Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Hide Arm/Group Description:
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-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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed 779
Measure Type: Count of Participants
Unit of Measure: Participants
Creatinine: All Grades Number Analyzed 737 participants
161
  21.8%
Creatinine: Grades 3-4 Number Analyzed 737 participants
2
   0.3%
Hyperbilirubinemia: All Grades Number Analyzed 734 participants
130
  17.7%
Hyperbilirubinemia: Grades 3-4 Number Analyzed 734 participants
9
   1.2%
AST: All Grades Number Analyzed 727 participants
342
  47.0%
AST: Grades 3-4 Number Analyzed 727 participants
12
   1.7%
ALT: All Grades Number Analyzed 736 participants
270
  36.7%
ALT: Grades 3-4 Number Analyzed 736 participants
10
   1.4%
Alkaline phosphatase: All Grades Number Analyzed 733 participants
465
  63.4%
Alkaline phosphatase: Grades 3-4 Number Analyzed 733 participants
23
   3.1%
6.Primary Outcome
Title Creatinine Clearance of Aflibercept Plus FOLFIRI
Hide Description 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).
Time Frame Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Overall number of participants analyzed = participants evaluable for this outcome measure.
Arm/Group Title Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Hide Arm/Group Description:
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-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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed 312
Mean (Standard Deviation)
Unit of Measure: mL/min
71.4  (29.3)
7.Primary Outcome
Title Number of Participants With Other Abnormal Biochemistry Parameters
Hide Description 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.
Time Frame Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Here, 'Number Analyzed' = participants with available data for specified categories.
Arm/Group Title Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Hide Arm/Group Description:
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-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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed 779
Measure Type: Count of Participants
Unit of Measure: Participants
Hypoglycemia: All Grades Number Analyzed 725 participants
90
  12.4%
Hypoglycemia: Grades 3-4 Number Analyzed 725 participants
6
   0.8%
Hyperglycemia: All Grades Number Analyzed 725 participants
403
  55.6%
Hyperglycemia: Grades 3-4 Number Analyzed 725 participants
30
   4.1%
Hypoalbuminemia: All Grades Number Analyzed 689 participants
241
  35.0%
Hypoalbuminemia: Grades 3-4 Number Analyzed 689 participants
6
   0.9%
8.Primary Outcome
Title Number of Participants With Abnormal Non-Gradable Biochemistry Parameters
Hide Description 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.
Time Frame Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Here, 'Number Analyzed = participants with available data for specified categories.
Arm/Group Title Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Hide Arm/Group Description:
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-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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed 779
Measure Type: Count of Participants
Unit of Measure: Participants
Chloride<LLN Number Analyzed 711 participants
135
  19.0%
Chloride>ULN Number Analyzed 711 participants
217
  30.5%
BUN<LLN Number Analyzed 258 participants
41
  15.9%
BUN>ULN Number Analyzed 258 participants
83
  32.2%
UREA<LLN Number Analyzed 591 participants
60
  10.2%
UREA>ULN Number Analyzed 591 participants
250
  42.3%
LDH<LLN Number Analyzed 723 participants
79
  10.9%
LDH>ULN Number Analyzed 723 participants
423
  58.5%
Total proteins<LLN Number Analyzed 711 participants
162
  22.8%
Total proteins>ULN Number Analyzed 711 participants
77
  10.8%
9.Primary Outcome
Title Number of Participants With Proteinuria Events
Hide Description 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.
Time Frame Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Hide Arm/Group Description:
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-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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed 779
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 1
286
  36.7%
Grade 2
123
  15.8%
Grade 3
54
   6.9%
Grade 4
5
   0.6%
10.Primary Outcome
Title Number of Participants With Proteinuria Grade >=2
Hide Description 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.
Time Frame Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Hide Arm/Group Description:
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-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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed 779
Measure Type: Number
Unit of Measure: participants
182
11.Primary Outcome
Title Number of Participants With Urinary Protein-Creatinine Ratio (UPCR)
Hide Description 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.
Time Frame Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Here, 'Number Analyzed = participants with available data for specified categories.
Arm/Group Title Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Hide Arm/Group Description:
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-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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed 779
Measure Type: Count of Participants
Unit of Measure: Participants
UPCR<=1 Number Analyzed 367 participants
265
  72.2%
UPCR>=1 to <=2 Number Analyzed 367 participants
51
  13.9%
UPCR>=2 to <=3 Number Analyzed 367 participants
24
   6.5%
UPCR>3 Number Analyzed 367 participants
27
   7.4%
12.Primary Outcome
Title Number of Participants With Proteinuria (Grade>=2) Concomitant With Hematuria and /or Hypertension
Hide Description 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.
Time Frame Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Hide Arm/Group Description:
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-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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed 779
Measure Type: Count of Participants
Unit of Measure: Participants
Proteinuria with hematuria
72
   9.2%
Proteinuria with hypertension
4
   0.5%
Proteinuria with hematuria and hypertension
3
   0.4%
13.Primary Outcome
Title Number of Participants With Cycle Delay and/or Dose Modification
Hide Description 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.
Time Frame Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population defined as the participants who signed the informed consent form and received at least one dose of study treatment.
Arm/Group Title Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Hide Arm/Group Description:
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-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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed 779
Measure Type: Count of Participants
Unit of Measure: Participants
No delay and no dose modification
119
  15.3%
Any delay and/or dose modification
660
  84.7%
Delay only
163
  20.9%
Delay and Aflibercept modified
39
   5.0%
Delay and FOLFIRI modified
308
  39.5%
Delay and Aflibercept and Folfiri modified
97
  12.5%
Only Aflibercept modified
5
   0.6%
Only FOLFIRI modified
43
   5.5%
Both Aflibercept and FOLFIRI modified
5
   0.6%
14.Secondary Outcome
Title 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
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
EORTC QLQ-C30 analysis population: participants who signed informed consent form; had an evaluable QLQ-C30 questionnaire at baseline and at least one evaluable assessment post baseline and received at least part of one dose of study treatment (either Aflibercept or FOLFIRI). Here, 'Number Analyzed' = participants analyzed at specified timepoints.
Arm/Group Title Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Hide Arm/Group Description:
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-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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed 636
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 630 participants
68.61  (20.48)
Change at Cycle 3 Number Analyzed 549 participants
-3.34  (18.83)
Change at Cycle 5 Number Analyzed 429 participants
-4.70  (18.89)
Change at Cycle 7 Number Analyzed 344 participants
-3.63  (22.02)
Change at Cycle 9 Number Analyzed 273 participants
-3.97  (21.31)
Change at Cycle 11 Number Analyzed 232 participants
-5.85  (22.26)
Change at Cycle 13 Number Analyzed 151 participants
-2.26  (21.69)
Change at Cycle 15 Number Analyzed 123 participants
-3.05  (22.46)
Change at Cycle 17 Number Analyzed 85 participants
-1.18  (22.50)
Change at Cycle 19 Number Analyzed 60 participants
-2.36  (22.92)
Change at Cycle 21 Number Analyzed 45 participants
-5.56  (23.77)
Change at Cycle 23 Number Analyzed 34 participants
-6.86  (19.94)
Change at Cycle 25 Number Analyzed 29 participants
-8.05  (16.89)
Change at Cycle 27 Number Analyzed 23 participants
-10.14  (17.58)
Change at Cycle 29 Number Analyzed 20 participants
-8.33  (14.05)
Change at Cycle 31 Number Analyzed 15 participants
-9.44  (16.92)
Change at Cycle 33 Number Analyzed 11 participants
-11.36  (21.82)
Change at Cycle 35 Number Analyzed 10 participants
-5.83  (20.81)
Change at EOT Number Analyzed 340 participants
-8.82  (23.95)
15.Secondary Outcome
Title Mean Change From Baseline in HRQL EORTC QLQ-C30 Score: Functional Scales
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
EORTC QLQ-C30 analysis population. Here, ‘Number Analyzed’ = participants analyzed at specified timepoints.
Arm/Group Title Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Hide Arm/Group Description:
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-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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed 636
Mean (Standard Deviation)
Unit of Measure: units on a scale
Physical - Baseline Number Analyzed 634 participants
81.79  (19.41)
Physical - Change at Cycle 3 Number Analyzed 551 participants
-3.73  (15.15)
Physical - Change at Cycle 5 Number Analyzed 439 participants
-3.95  (15.22)
Physical - Change at Cycle 7 Number Analyzed 342 participants
-4.62  (16.23)
Physical - Change at Cycle 9 Number Analyzed 275 participants
-4.36  (15.79)
Physical - Change at Cycle 11 Number Analyzed 235 participants
-6.99  (17.89)
Physical - Change at Cycle 13 Number Analyzed 154 participants
-4.99  (16.17)
Physical - Change at Cycle 15 Number Analyzed 122 participants
-3.54  (15.99)
Physical - Change at Cycle 17 Number Analyzed 87 participants
-5.10  (16.20)
Physical - Change at Cycle 19 Number Analyzed 61 participants
-5.68  (16.23)
Physical - Change at Cycle 21 Number Analyzed 46 participants
-5.70  (13.01)
Physical - Change at Cycle 23 Number Analyzed 36 participants
-7.87  (14.38)
Physical - Change at Cycle 25 Number Analyzed 29 participants
-5.75  (12.18)
Physical - Change at Cycle 27 Number Analyzed 23 participants
-6.59  (11.64)
Physical - Change at Cycle 29 Number Analyzed 20 participants
-7.67  (11.09)
Physical - Change at Cycle 31 Number Analyzed 15 participants
-9.33  (14.65)
Physical - Change at Cycle 33 Number Analyzed 11 participants
-5.45  (9.81)
Physical - Change at Cycle 35 Number Analyzed 10 participants
-10.00  (13.05)
Physical - Change at EOT Number Analyzed 341 participants
-11.16  (21.65)
Role - Baseline Number Analyzed 633 participants
79.91  (26.25)
Role - Change at Cycle 3 Number Analyzed 551 participants
-6.26  (25.22)
Role - Change at Cycle 5 Number Analyzed 442 participants
-5.66  (23.26)
Role - Change at Cycle 7 Number Analyzed 342 participants
-6.68  (24.29)
Role - Change at Cycle 9 Number Analyzed 275 participants
-6.55  (23.95)
Role - Change at Cycle 11 Number Analyzed 234 participants
-8.76  (26.35)
Role - Change at Cycle 13 Number Analyzed 154 participants
-7.36  (23.41)
Role - Change at Cycle 15 Number Analyzed 123 participants
-7.18  (21.98)
Role - Change at Cycle 17 Number Analyzed 87 participants
-9.58  (22.54)
Role - Change at Cycle 19 Number Analyzed 61 participants
-9.84  (22.44)
Role - Change at Cycle 21 Number Analyzed 46 participants
-9.78  (18.11)
Role - Change at Cycle 23 Number Analyzed 36 participants
-10.65  (18.32)
Role - Change at Cycle 25 Number Analyzed 29 participants
-10.92  (17.97)
Role - Change at Cycle 27 Number Analyzed 23 participants
-10.14  (17.22)
Role - Change at Cycle 29 Number Analyzed 20 participants
-10.83  (17.33)
Role - Change at Cycle 31 Number Analyzed 15 participants
-14.44  (18.76)
Role - Change at Cycle 33 Number Analyzed 11 participants
-15.15  (15.73)
Role - Change at Cycle 35 Number Analyzed 10 participants
-15.00  (16.57)
Role - Change at EOT Number Analyzed 340 participants
-12.11  (28.22)
Emotional - Baseline Number Analyzed 634 participants
78.96  (20.60)
Emotional - Change at Cycle 3 Number Analyzed 553 participants
1.14  (19.95)
Emotional - Change at Cycle 5 Number Analyzed 436 participants
0.74  (19.32)
Emotional - Change at Cycle 7 Number Analyzed 344 participants
1.58  (20.91)
Emotional - Change at Cycle 9 Number Analyzed 275 participants
1.69  (21.38)
Emotional - Change at Cycle 11 Number Analyzed 235 participants
0.08  (20.40)
Emotional - Change at Cycle 13 Number Analyzed 152 participants
0.93  (20.08)
Emotional - Change at Cycle 15 Number Analyzed 124 participants
2.51  (20.23)
Emotional - Change at Cycle 17 Number Analyzed 87 participants
2.91  (18.23)
Emotional - Change at Cycle 19 Number Analyzed 60 participants
1.39  (17.60)
Emotional - Change at Cycle 21 Number Analyzed 44 participants
0.06  (17.86)
Emotional - Change at Cycle 23 Number Analyzed 35 participants
1.75  (19.29)
Emotional - Change at Cycle 25 Number Analyzed 29 participants
4.98  (15.86)
Emotional - Change at Cycle 27 Number Analyzed 23 participants
1.57  (17.64)
Emotional - Change at Cycle 29 Number Analyzed 20 participants
2.64  (17.88)
Emotional - Change at Cycle 31 Number Analyzed 15 participants
1.30  (17.78)
Emotional - Change at Cycle 33 Number Analyzed 11 participants
0.25  (3.82)
Emotional - Change at Cycle 35 Number Analyzed 10 participants
-0.00  (5.56)
Emotional - Change at EOT Number Analyzed 345 participants
-2.87  (22.52)
Cognitive - Baseline Number Analyzed 635 participants
86.90  (19.26)
Cognitive - Change at Cycle 3 Number Analyzed 555 participants
-1.77  (16.92)
Cognitive - Change at Cycle 5 Number Analyzed 437 participants
-1.87  (16.58)
Cognitive - Change at Cycle 7 Number Analyzed 343 participants
-1.99  (19.71)
Cognitive - Change at Cycle 9 Number Analyzed 275 participants
-2.18  (20.17)
Cognitive - Change at Cycle 11 Number Analyzed 234 participants
-4.27  (20.29)
Cognitive - Change at Cycle 13 Number Analyzed 153 participants
-2.83  (17.40)
Cognitive - Change at Cycle 15 Number Analyzed 124 participants
-2.28  (19.40)
Cognitive - Change at Cycle 17 Number Analyzed 87 participants
-3.45  (19.38)
Cognitive - Change at Cycle 19 Number Analyzed 60 participants
-5.00  (22.19)
Cognitive - Change at Cycle 21 Number Analyzed 45 participants
-5.56  (16.28)
Cognitive - Change at Cycle 23 Number Analyzed 35 participants
-5.71  (14.54)
Cognitive - Change at Cycle 25 Number Analyzed 29 participants
-6.90  (21.14)
Cognitive - Change at Cycle 27 Number Analyzed 23 participants
-5.80  (16.37)
Cognitive - Change at Cycle 29 Number Analyzed 20 participants
-6.67  (18.26)
Cognitive - Change at Cycle 31 Number Analyzed 15 participants
-5.56  (15.00)
Cognitive - Change at Cycle 33 Number Analyzed 11 participants
-10.61  (17.12)
Cognitive - Change at Cycle 35 Number Analyzed 10 participants
-11.67  (13.72)
Cognitive- Change at EOT Number Analyzed 345 participants
-4.98  (22.67)
Social - Baseline Number Analyzed 634 participants
80.57  (24.68)
Social - Change at Cycle 3 Number Analyzed 554 participants
-2.05  (22.83)
Social - Change at Cycle 5 Number Analyzed 437 participants
-2.86  (21.60)
Social - Change at Cycle 7 Number Analyzed 345 participants
-4.78  (23.65)
Social - Change at Cycle 9 Number Analyzed 274 participants
-4.56  (23.84)
Social - Change at Cycle 11 Number Analyzed 235 participants
-7.09  (24.83)
Social - Change at Cycle 13 Number Analyzed 153 participants
-5.56  (24.03)
Social - Change at Cycle 15 Number Analyzed 124 participants
-6.18  (23.23)
Social - Change at Cycle 17 Number Analyzed 87 participants
-5.56  (22.69)
Social - Change at Cycle 19 Number Analyzed 60 participants
-5.28  (22.02)
Social - Change at Cycle 21 Number Analyzed 45 participants
-5.56  (21.61)
Social - Change at Cycle 23 Number Analyzed 35 participants
-7.62  (17.78)
Social - Change at Cycle 25 Number Analyzed 29 participants
-4.60  (18.31)
Social - Change at Cycle 27 Number Analyzed 23 participants
-2.17  (17.63)
Social - Change at Cycle 29 Number Analyzed 20 participants
-5.00  (18.81)
Social - Change at Cycle 31 Number Analyzed 15 participants
-7.78  (25.09)
Social - Change at Cycle 33 Number Analyzed 11 participants
-1.52  (17.41)
Social - Change at Cycle 35 Number Analyzed 10 participants
-1.67  (14.59)
Social - Change at EOT Number Analyzed 344 participants
-9.01  (26.23)
16.Secondary Outcome
Title Change From Baseline in HRQL EORTC QLQ-C30 Score: Symptom Scales
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
EORTC QLQ-C30 analysis population. Here, "Number Analyzed = participants analyzed at specified timepoints.
Arm/Group Title Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Hide Arm/Group Description:
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-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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed 636
Mean (Standard Deviation)
Unit of Measure: units on a scale
Fatigue - Baseline Number Analyzed 633 participants
29.16  (23.48)
Fatigue - Change at Cycle 3 Number Analyzed 551 participants
7.35  (21.62)
Fatigue - Change at Cycle 5 Number Analyzed 443 participants
8.40  (21.88)
Fatigue - Change at Cycle 7 Number Analyzed 344 participants
9.54  (22.60)
Fatigue - Change at Cycle 9 Number Analyzed 276 participants
7.89  (21.80)
Fatigue - Change at Cycle 11 Number Analyzed 235 participants
11.30  (23.73)
Fatigue - Change at Cycle 13 Number Analyzed 154 participants
8.33  (21.72)
Fatigue - Change at Cycle 15 Number Analyzed 123 participants
7.41  (22.38)
Fatigue - Change at Cycle 17 Number Analyzed 87 participants
6.70  (21.25)
Fatigue - Change at Cycle 19 Number Analyzed 61 participants
8.93  (19.83)
Fatigue - Change at Cycle 21 Number Analyzed 46 participants
10.39  (17.90)
Fatigue - Change at Cycle 23 Number Analyzed 36 participants
10.80  (18.49)
Fatigue - Change at Cycle 25 Number Analyzed 29 participants
7.66  (19.94)
Fatigue - Change at Cycle 27 Number Analyzed 23 participants
9.66  (18.74)
Fatigue - Change at Cycle 29 Number Analyzed 20 participants
11.67  (18.55)
Fatigue - Change at Cycle 31 Number Analyzed 15 participants
14.07  (21.61)
Fatigue - Change at Cycle 33 Number Analyzed 11 participants
15.15  (21.81)
Fatigue - Change at Cycle 35 Number Analyzed 10 participants
14.44  (18.92)
Fatigue - Change at EOT Number Analyzed 343 participants
12.31  (25.56)
Nausea and Vomiting - Baseline Number Analyzed 635 participants
5.88  (13.99)
Nausea and Vomiting - Change at Cycle 3 Number Analyzed 554 participants
6.68  (19.81)
Nausea and Vomiting - Change at Cycle 5 Number Analyzed 442 participants
6.98  (19.79)
Nausea and Vomiting - Change at Cycle 7 Number Analyzed 343 participants
6.61  (18.07)
Nausea and Vomiting - Change at Cycle 9 Number Analyzed 277 participants
6.20  (19.68)
Nausea and Vomiting - Change at Cycle 11 Number Analyzed 236 participants
8.97  (19.83)
Nausea and Vomiting - Change at Cycle 13 Number Analyzed 154 participants
6.82  (14.71)
Nausea and Vomiting - Change at Cycle 15 Number Analyzed 124 participants
6.85  (16.33)
Nausea and Vomiting - Change at Cycle 17 Number Analyzed 87 participants
3.45  (15.49)
Nausea and Vomiting - Change at Cycle 19 Number Analyzed 61 participants
6.56  (14.04)
Nausea and Vomiting - Change at Cycle 21 Number Analyzed 46 participants
3.99  (14.14)
Nausea and Vomiting - Change at Cycle 23 Number Analyzed 36 participants
7.87  (10.90)
Nausea and Vomiting - Change at Cycle 25 Number Analyzed 29 participants
4.02  (8.52)
Nausea and Vomiting - Change at Cycle 27 Number Analyzed 23 participants
7.25  (11.04)
Nausea and Vomiting - Change at Cycle 29 Number Analyzed 20 participants
1.67  (5.13)
Nausea and Vomiting - Change at Cycle 31 Number Analyzed 15 participants
13.33  (28.31)
Nausea and Vomiting - Change at Cycle 33 Number Analyzed 11 participants
3.03  (6.74)
Nausea and Vomiting - Change at Cycle 35 Number Analyzed 10 participants
3.33  (7.03)
Nausea and Vomiting - Change at EOT Number Analyzed 344 participants
6.64  (21.11)
Pain - Baseline Number Analyzed 636 participants
20.47  (25.08)
Pain - Change at Cycle 3 Number Analyzed 554 participants
2.68  (25.02)
Pain - Change at Cycle 5 Number Analyzed 444 participants
2.52  (23.48)
Pain - Change at Cycle 7 Number Analyzed 345 participants
3.00  (24.98)
Pain - Change at Cycle 9 Number Analyzed 276 participants
2.72  (24.45)
Pain - Change at Cycle 11 Number Analyzed 236 participants
6.64  (23.68)
Pain - Change at Cycle 13 Number Analyzed 155 participants
5.16  (19.79)
Pain - Change at Cycle 15 Number Analyzed 124 participants
7.26  (21.91)
Pain - Change at Cycle 17 Number Analyzed 87 participants
9.39  (22.97)
Pain - Change at Cycle 19 Number Analyzed 61 participants
8.74  (22.28)
Pain - Change at Cycle 21 Number Analyzed 46 participants
7.25  (18.14)
Pain - Change at Cycle 23 Number Analyzed 36 participants
8.33  (19.31)
Pain - Change at Cycle 25 Number Analyzed 29 participants
5.75  (21.02)
Pain - Change at Cycle 27 Number Analyzed 23 participants
5.07  (17.72)
Pain - Change at Cycle 29 Number Analyzed 20 participants
4.17  (16.11)
Pain - Change at Cycle 31 Number Analyzed 15 participants
10.00  (23.40)
Pain - Change at Cycle 33 Number Analyzed 11 participants
7.58  (22.81)
Pain - Change at Cycle 35 Number Analyzed 10 participants
6.67  (21.08)
Pain - Change at EOT Number Analyzed 347 participants
10.85  (28.99)
Dyspnoea - Baseline Number Analyzed 627 participants
13.45  (22.01)
Dyspnoea - Change at Cycle 3 Number Analyzed 542 participants
3.63  (22.96)
Dyspnoea - Change at Cycle 5 Number Analyzed 435 participants
5.75  (24.06)
Dyspnoea - Change at Cycle 7 Number Analyzed 339 participants
6.98  (24.47)
Dyspnoea - Change at Cycle 9 Number Analyzed 271 participants
6.89  (24.38)
Dyspnoea - Change at Cycle 11 Number Analyzed 232 participants
8.19  (26.59)
Dyspnoea - Change at Cycle 13 Number Analyzed 152 participants
6.36  (25.37)
Dyspnoea - Change at Cycle 15 Number Analyzed 121 participants
3.58  (24.65)
Dyspnoea - Change at Cycle 17 Number Analyzed 84 participants
5.16  (24.54)
Dyspnoea - Change at Cycle 19 Number Analyzed 59 participants
6.78  (26.82)
Dyspnoea - Change at Cycle 21 Number Analyzed 44 participants
3.79  (22.98)
Dyspnoea - Change at Cycle 23 Number Analyzed 33 participants
4.04  (20.00)
Dyspnoea - Change at Cycle 25 Number Analyzed 27 participants
1.23  (21.64)
Dyspnoea - Change at Cycle 27 Number Analyzed 22 participants
3.03  (22.79)
Dyspnoea - Change at Cycle 29 Number Analyzed 19 participants
-1.75  (23.50)
Dyspnoea - Change at Cycle 31 Number Analyzed 14 participants
16.67  (28.50)
Dyspnoea - Change at Cycle 33 Number Analyzed 10 participants
16.67  (17.57)
Dyspnoea - Change at Cycle 35 Number Analyzed 10 participants
16.67  (23.57)
Dyspnoea - Change at EOT Number Analyzed 337 participants
6.53  (25.79)
Insomnia - Baseline Number Analyzed 628 participants
24.15  (28.09)
Insomnia - Change at Cycle 3 Number Analyzed 544 participants
0.37  (27.36)
Insomnia - Change at Cycle 5 Number Analyzed 438 participants
-0.08  (28.48)
Insomnia - Change at Cycle 7 Number Analyzed 338 participants
-2.37  (29.63)
Insomnia - Change at Cycle 9 Number Analyzed 274 participants
-0.24  (29.37)
Insomnia - Change at Cycle 11 Number Analyzed 234 participants
2.56  (28.86)
Insomnia - Change at Cycle 13 Number Analyzed 153 participants
0.65  (26.89)
Insomnia - Change at Cycle 15 Number Analyzed 122 participants
-2.19  (27.01)
Insomnia - Change at Cycle 17 Number Analyzed 87 participants
-1.92  (25.60)
Insomnia - Change at Cycle 19 Number Analyzed 61 participants
1.64  (23.12)
Insomnia - Change at Cycle 21 Number Analyzed 45 participants
0.74  (25.11)
Insomnia - Change at Cycle 23 Number Analyzed 36 participants
-0.93  (33.32)
Insomnia - Change at Cycle 25 Number Analyzed 29 participants
-0.00  (28.17)
Insomnia - Change at Cycle 27 Number Analyzed 22 participants
-1.52  (24.07)
Insomnia - Change at Cycle 29 Number Analyzed 20 participants
-3.33  (30.40)
Insomnia - Change at Cycle 31 Number Analyzed 15 participants
-4.44  (41.53)
Insomnia - Change at Cycle 33 Number Analyzed 11 participants
-6.06  (32.72)
Insomnia - Change at Cycle 35 Number Analyzed 10 participants
-3.33  (33.15)
Insomnia - Change at EOT Number Analyzed 339 participants
5.31  (32.50)
Appetite loss - Baseline Number Analyzed 631 participants
17.38  (26.01)
Appetite loss - Change at Cycle 3 Number Analyzed 546 participants
9.10  (28.64)
Appetite loss - Change at Cycle 5 Number Analyzed 436 participants
9.02  (28.14)
Appetite loss - Change at Cycle 7 Number Analyzed 342 participants
9.84  (27.80)
Appetite loss - Change at Cycle 9 Number Analyzed 274 participants
9.98  (27.18)
Appetite loss - Change at Cycle 11 Number Analyzed 234 participants
14.53  (28.27)
Appetite loss - Change at Cycle 13 Number Analyzed 150 participants
10.67  (27.12)
Appetite loss - Change at Cycle 15 Number Analyzed 121 participants
10.74  (25.90)
Appetite loss - Change at Cycle 17 Number Analyzed 86 participants
8.91  (24.75)
Appetite loss - Change at Cycle 19 Number Analyzed 61 participants
9.84  (24.60)
Appetite loss - Change at Cycle 21 Number Analyzed 46 participants
13.04  (25.80)
Appetite loss - Change at Cycle 23 Number Analyzed 35 participants
12.38  (25.67)
Appetite loss - Change at Cycle 25 Number Analyzed 29 participants
11.49  (20.46)
Appetite loss - Change at Cycle 27 Number Analyzed 23 participants
15.94  (22.18)
Appetite loss - Change at Cycle 29 Number Analyzed 20 participants
15.00  (20.16)
Appetite loss - Change at Cycle 31 Number Analyzed 15 participants
15.56  (24.77)
Appetite loss - Change at Cycle 33 Number Analyzed 11 participants
15.15  (22.92)
Appetite loss - Change at Cycle 35 Number Analyzed 10 participants
16.67  (17.57)
Appetite loss - Change at EOT Number Analyzed 338 participants
12.03  (33.48)
Constipation - Baseline Number Analyzed 632 participants
12.71  (21.61)
Constipation - Change at Cycle 3 Number Analyzed 550 participants
2.42  (25.25)
Constipation - Change at Cycle 5 Number Analyzed 433 participants
3.77  (26.52)
Constipation - Change at Cycle 7 Number Analyzed 342 participants
2.63  (26.09)
Constipation - Change at Cycle 9 Number Analyzed 274 participants
5.35  (26.68)
Constipation - Change at Cycle 11 Number Analyzed 234 participants
4.42  (26.47)
Constipation - Change at Cycle 13 Number Analyzed 153 participants
4.58  (25.95)
Constipation - Change at Cycle 15 Number Analyzed 122 participants
4.92  (26.30)
Constipation - Change at Cycle 17 Number Analyzed 86 participants
5.43  (23.35)
Constipation - Change at Cycle 19 Number Analyzed 60 participants
8.33  (21.81)
Constipation - Change at Cycle 21 Number Analyzed 44 participants
6.06  (18.00)
Constipation - Change at Cycle 23 Number Analyzed 36 participants
9.26  (21.98)
Constipation - Change at Cycle 25 Number Analyzed 29 participants
5.75  (17.97)
Constipation - Change at Cycle 27 Number Analyzed 23 participants
1.45  (12.22)
Constipation - Change at Cycle 29 Number Analyzed 20 participants
6.67  (20.52)
Constipation - Change at Cycle 31 Number Analyzed 15 participants
22.22  (32.53)
Constipation - Change at Cycle 33 Number Analyzed 11 participants
12.12  (16.82)
Constipation - Change at Cycle 35 Number Analyzed 10 participants
10.00  (16.10)
Constipation - Change at EOT Number Analyzed 344 participants
3.78  (27.33)
Diarrhoea - Baseline Number Analyzed 633 participants
10.37  (19.47)
Diarrhoea - Change at Cycle 3 Number Analyzed 549 participants
11.72  (28.16)
Diarrhoea - Change at Cycle 5 Number Analyzed 433 participants
10.85  (28.29)
Diarrhoea - Change at Cycle 7 Number Analyzed 344 participants
14.63  (29.94)
Diarrhoea - Change at Cycle 9 Number Analyzed 274 participants
11.44  (26.44)
Diarrhoea - Change at Cycle 11 Number Analyzed 235 participants
15.46  (27.26)
Diarrhoea - Change at Cycle 13 Number Analyzed 151 participants
11.26  (24.00)
Diarrhoea - Change at Cycle 15 Number Analyzed 121 participants
11.02  (28.02)
Diarrhoea - Change at Cycle 17 Number Analyzed 87 participants
10.34  (21.75)
Diarrhoea - Change at Cycle 19 Number Analyzed 59 participants
15.25  (25.76)
Diarrhoea - Change at Cycle 21 Number Analyzed 45 participants
14.07  (24.09)
Diarrhoea - Change at Cycle 23 Number Analyzed 36 participants
18.52  (21.74)
Diarrhoea - Change at Cycle 25 Number Analyzed 29 participants
10.34  (22.01)
Diarrhoea - Change at Cycle 27 Number Analyzed 22 participants
13.64  (19.68)
Diarrhoea - Change at Cycle 29 Number Analyzed 20 participants
16.67  (25.36)
Diarrhoea - Change at Cycle 31 Number Analyzed 15 participants
20.00  (24.56)
Diarrhoea - Change at Cycle 33 Number Analyzed 11 participants
18.18  (22.92)
Diarrhoea - Change at Cycle 35 Number Analyzed 10 participants
30.00  (18.92)
Diarrhoea - Change at EOT Number Analyzed 342 participants
7.31  (24.26)
Financial difficulties - Baseline Number Analyzed 628 participants
20.12  (30.25)
Financial difficulties - Change at Cycle 3 Number Analyzed 547 participants
-1.83  (23.80)
Financial difficulties - Change at Cycle 5 Number Analyzed 430 participants
-1.32  (24.00)
Financial difficulties - Change at Cycle 7 Number Analyzed 337 participants
-0.99  (27.68)
Financial difficulties - Change at Cycle 9 Number Analyzed 270 participants
-0.49  (26.80)
Financial difficulties - Change at Cycle 11 Number Analyzed 232 participants
3.30  (25.64)
Financial difficulties - Change at Cycle 13 Number Analyzed 150 participants
1.11  (27.96)
Financial difficulties - Change at Cycle 15 Number Analyzed 122 participants
-0.27  (27.94)
Financial difficulties - Change at Cycle 17 Number Analyzed 87 participants
0.77  (27.36)
Financial difficulties - Change at Cycle 19 Number Analyzed 60 participants
1.67  (29.70)
Financial difficulties - Change at Cycle 21 Number Analyzed 45 participants
4.44  (25.23)
Financial difficulties - Change at Cycle 23 Number Analyzed 34 participants
2.94  (23.74)
Financial difficulties - Change at Cycle 25 Number Analyzed 29 participants
-4.60  (19.36)
Financial difficulties - Change at Cycle 27 Number Analyzed 23 participants
-2.90  (24.44)
Financial difficulties - Change at Cycle 29 Number Analyzed 20 participants
0.00  (21.63)
Financial difficulties - Change at Cycle 31 Number Analyzed 15 participants
-2.22  (19.79)
Financial difficulties - Change at Cycle 33 Number Analyzed 11 participants
-3.03  (17.98)
Financial difficulties - Change at Cycle 35 Number Analyzed 10 participants
0.00  (15.71)
Financial difficulties - Change at EOT Number Analyzed 337 participants
2.97  (27.90)
17.Secondary Outcome
Title Change From Baseline in HRQL EQ-5D-3L Quality of Life: Single Index Utility Score
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
EQ-5D analysis population: participants who signed informed consent form, had an evaluable EQ-5D questionnaire at baseline and at least one evaluable assessment post baseline and received at least part of one dose of study treatment (either Aflibercept or FOLFIRI). Here, 'Number Analyzed' = participants analyzed at specified timepoints.
Arm/Group Title Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Hide Arm/Group Description:
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-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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed 623
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 623 participants
0.77  (0.24)
Change at Cycle 3 Number Analyzed 536 participants
-0.02  (0.23)
Change at Cycle 5 Number Analyzed 428 participants
-0.03  (0.22)
Change at Cycle 7 Number Analyzed 335 participants
-0.04  (0.23)
Change at Cycle 9 Number Analyzed 269 participants
-0.05  (0.24)
Change at Cycle 11 Number Analyzed 226 participants
-0.07  (0.25)
Change at Cycle 13 Number Analyzed 149 participants
-0.05  (0.20)
Change at Cycle 15 Number Analyzed 119 participants
-0.06  (0.23)
Change at Cycle 17 Number Analyzed 81 participants
-0.05  (0.24)
Change at Cycle 19 Number Analyzed 58 participants
-0.05  (0.18)
Change at Cycle 21 Number Analyzed 44 participants
-0.09  (0.20)
Change at Cycle 23 Number Analyzed 34 participants
-0.14  (0.26)
Change at Cycle 25 Number Analyzed 28 participants
-0.08  (0.21)
Change at Cycle 27 Number Analyzed 23 participants
-0.08  (0.21)
Change at Cycle 29 Number Analyzed 20 participants
-0.08  (0.20)
Change at Cycle 31 Number Analyzed 15 participants
-0.12  (0.30)
Change at Cycle 33 Number Analyzed 11 participants
0.02  (0.14)
Change at Cycle 35 Number Analyzed 10 participants
-0.05  (0.14)
Change at EOT Number Analyzed 343 participants
-0.11  (0.30)
18.Secondary Outcome
Title Change From Baseline in HRQL EQ-5D-3L VAS Score
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
EQ-5D analysis population. Here, 'Number Analyzed' = participants analyzed at specified timepoints.
Arm/Group Title Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Hide Arm/Group Description:
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-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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed 623
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 577 participants
72.81  (18.28)
Change at Cycle 3 Number Analyzed 482 participants
-1.85  (15.35)
Change at Cycle 5 Number Analyzed 381 participants
-2.15  (14.31)
Change at Cycle 7 Number Analyzed 303 participants
-2.20  (16.33)
Change at Cycle 9 Number Analyzed 236 participants
-2.74  (14.28)
Change at Cycle 11 Number Analyzed 203 participants
-3.10  (14.40)
Change at Cycle 13 Number Analyzed 134 participants
-2.36  (15.29)
Change at Cycle 15 Number Analyzed 103 participants
-1.05  (15.51)
Change at Cycle 17 Number Analyzed 74 participants
-1.91  (13.54)
Change at Cycle 19 Number Analyzed 52 participants
-3.06  (13.85)
Change at Cycle 21 Number Analyzed 38 participants
-2.13  (14.98)
Change at Cycle 23 Number Analyzed 30 participants
-5.77  (13.50)
Change at Cycle 25 Number Analyzed 25 participants
-7.28  (10.53)
Change at Cycle 27 Number Analyzed 17 participants
-4.94  (8.68)
Change at Cycle 29 Number Analyzed 15 participants
-8.80  (10.12)
Change at Cycle 31 Number Analyzed 13 participants
-6.69  (12.61)
Change at Cycle 33 Number Analyzed 10 participants
-7.90  (13.08)
Change at Cycle 35 Number Analyzed 8 participants
-8.88  (11.53)
Change at EOT Number Analyzed 310 participants
-6.67  (17.38)
Time Frame All AEs were collected from signature of the informed consent form up to the final visit (214 weeks) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'on-treatment period’ (from the first dose of treatment to 30 days after the last dose of treatment [either aflibercept or FOLFIRI]). Analysis was performed on safety population.
 
Arm/Group Title Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Hide Arm/Group Description 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-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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
All-Cause Mortality
Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Affected / at Risk (%)
Total   48/779 (6.16%) 
Show Serious Adverse Events Hide Serious Adverse Events
Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Affected / at Risk (%)
Total   272/779 (34.92%) 
Blood and lymphatic system disorders   
Anaemia  1  7/779 (0.90%) 
Febrile Neutropenia  1  12/779 (1.54%) 
Neutropenia  1  14/779 (1.80%) 
Thrombocytopenia  1  1/779 (0.13%) 
Thrombotic Microangiopathy  1  1/779 (0.13%) 
Cardiac disorders   
Acute Myocardial Infarction  1  2/779 (0.26%) 
Angina Pectoris  1  2/779 (0.26%) 
Atrial Fibrillation  1  1/779 (0.13%) 
Atrial Flutter  1  2/779 (0.26%) 
Atrial Thrombosis  1  1/779 (0.13%) 
Cardiac Failure  1  1/779 (0.13%) 
Cardiac Failure Congestive  1  1/779 (0.13%) 
Cardio-Respiratory Arrest  1  1/779 (0.13%) 
Coronary Artery Thrombosis  1  1/779 (0.13%) 
Supraventricular Tachycardia  1  2/779 (0.26%) 
Ventricular Tachycardia  1  1/779 (0.13%) 
Eye disorders   
Retinal Detachment  1  1/779 (0.13%) 
Gastrointestinal disorders   
Abdominal Pain  1  8/779 (1.03%) 
Abdominal Pain Upper  1  4/779 (0.51%) 
Anal Fissure  1  1/779 (0.13%) 
Anal Fistula  1  1/779 (0.13%) 
Anorectal Ulcer  1  1/779 (0.13%) 
Ascites  1  1/779 (0.13%) 
Colitis  1  2/779 (0.26%) 
Constipation  1  1/779 (0.13%) 
Diarrhoea  1  39/779 (5.01%) 
Duodenal Ulcer Haemorrhage  1  1/779 (0.13%) 
Enteritis  1  2/779 (0.26%) 
Enterocutaneous Fistula  1  4/779 (0.51%) 
Enterovesical Fistula  1  1/779 (0.13%) 
Faecaloma  1  1/779 (0.13%) 
Fistula Of Small Intestine  1  1/779 (0.13%) 
Gastrointestinal Fistula  1  1/779 (0.13%) 
Gastrointestinal Haemorrhage  1  1/779 (0.13%) 
Gastrointestinal Hypomotility  1  1/779 (0.13%) 
Gastrointestinal Perforation  1  1/779 (0.13%) 
Gingival Bleeding  1  1/779 (0.13%) 
Haematemesis  1  1/779 (0.13%) 
Haemorrhoids  1  2/779 (0.26%) 
Haemorrhoids Thrombosed  1  1/779 (0.13%) 
Ileus  1  2/779 (0.26%) 
Ileus Paralytic  1  1/779 (0.13%) 
Inguinal Hernia  1  1/779 (0.13%) 
Intestinal Obstruction  1  12/779 (1.54%) 
Intestinal Perforation  1  4/779 (0.51%) 
Large Intestine Perforation  1  4/779 (0.51%) 
Lower Gastrointestinal Haemorrhage  1  1/779 (0.13%) 
Melaena  1  1/779 (0.13%) 
Nausea  1  1/779 (0.13%) 
Odynophagia  1  1/779 (0.13%) 
Oesophagitis  1  1/779 (0.13%) 
Proctalgia  1  1/779 (0.13%) 
Proctitis  1  1/779 (0.13%) 
Rectal Haemorrhage  1  2/779 (0.26%) 
Rectal Perforation  1  1/779 (0.13%) 
Rectal Tenesmus  1  1/779 (0.13%) 
Small Intestinal Obstruction  1  4/779 (0.51%) 
Stomatitis  1  9/779 (1.16%) 
Subileus  1  1/779 (0.13%) 
Vomiting  1  10/779 (1.28%) 
General disorders   
Asthenia  1  2/779 (0.26%) 
Chest Pain  1  1/779 (0.13%) 
Disease Progression  1  23/779 (2.95%) 
Fatigue  1  4/779 (0.51%) 
General Physical Health Deterioration  1  5/779 (0.64%) 
Malaise  1  1/779 (0.13%) 
Multiple Organ Dysfunction Syndrome  1  1/779 (0.13%) 
Pain  1  1/779 (0.13%) 
Pyrexia  1  12/779 (1.54%) 
Sudden Death  1  2/779 (0.26%) 
Hepatobiliary disorders   
Cholangitis  1  2/779 (0.26%) 
Cholecystitis  1  2/779 (0.26%) 
Cholecystitis Acute  1  1/779 (0.13%) 
Cholelithiasis  1  1/779 (0.13%) 
Cholestasis  1  1/779 (0.13%) 
Hepatic Failure  1  1/779 (0.13%) 
Jaundice Cholestatic  1  1/779 (0.13%) 
Portal Hypertension  1  1/779 (0.13%) 
Immune system disorders   
Anaphylactic Shock  1  1/779 (0.13%) 
Infections and infestations   
Abdominal Abscess  1  2/779 (0.26%) 
Abdominal Infection  1  1/779 (0.13%) 
Abdominal Wall Abscess  1  1/779 (0.13%) 
Bronchitis  1  3/779 (0.39%) 
Catheter Site Abscess  1  1/779 (0.13%) 
Device Related Infection  1  7/779 (0.90%) 
Diabetic Foot Infection  1  1/779 (0.13%) 
Escherichia Urinary Tract Infection  1  1/779 (0.13%) 
Febrile Infection  1  1/779 (0.13%) 
Gastroenteritis  1  1/779 (0.13%) 
Gastroenteritis Escherichia Coli  1  1/779 (0.13%) 
Herpes Zoster  1  1/779 (0.13%) 
Herpes Zoster Meningoencephalitis  1  1/779 (0.13%) 
Infection  1  5/779 (0.64%) 
Infective Myositis  1  1/779 (0.13%) 
Klebsiella Infection  1  1/779 (0.13%) 
Localised Infection  1  1/779 (0.13%) 
Lower Respiratory Tract Infection  1  3/779 (0.39%) 
Lung Infection  1  3/779 (0.39%) 
Neutropenic Infection  1  1/779 (0.13%) 
Neutropenic Sepsis  1  3/779 (0.39%) 
Parainfluenzae Virus Infection  1  1/779 (0.13%) 
Pelvic Abscess  1  1/779 (0.13%) 
Periodontitis  1  1/779 (0.13%) 
Pharyngitis  1  1/779 (0.13%) 
Phlebitis Infective  1  1/779 (0.13%) 
Pneumonia  1  8/779 (1.03%) 
Pyelonephritis  1  1/779 (0.13%) 
Rectal Abscess  1  1/779 (0.13%) 
Respiratory Tract Infection  1  3/779 (0.39%) 
Sepsis  1  7/779 (0.90%) 
Septic Shock  1  2/779 (0.26%) 
Sinusitis  1  1/779 (0.13%) 
Streptococcal Bacteraemia  1  1/779 (0.13%) 
Tracheobronchitis  1  2/779 (0.26%) 
Tuberculosis  1  1/779 (0.13%) 
Upper Respiratory Tract Infection  1  1/779 (0.13%) 
Urinary Tract Infection  1  5/779 (0.64%) 
Urosepsis  1  1/779 (0.13%) 
Injury, poisoning and procedural complications   
Accidental Exposure To Product  1  2/779 (0.26%) 
Accidental Overdose  1  1/779 (0.13%) 
Anastomotic Leak  1  1/779 (0.13%) 
Contrast Media Reaction  1  1/779 (0.13%) 
Gastrointestinal Stoma Complication  1  1/779 (0.13%) 
Hip Fracture  1  1/779 (0.13%) 
Meniscus Injury  1  1/779 (0.13%) 
Stoma Site Haemorrhage  1  1/779 (0.13%) 
Investigations   
Alanine Aminotransferase Increased  1  1/779 (0.13%) 
Metabolism and nutrition disorders   
Decreased Appetite  1  1/779 (0.13%) 
Dehydration  1  5/779 (0.64%) 
Hypercalcaemia  1  1/779 (0.13%) 
Hyponatraemia  1  1/779 (0.13%) 
Musculoskeletal and connective tissue disorders   
Back Pain  1  2/779 (0.26%) 
Musculoskeletal Chest Pain  1  1/779 (0.13%) 
Musculoskeletal Pain  1  1/779 (0.13%) 
Neck Pain  1  1/779 (0.13%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Cancer Pain  1  1/779 (0.13%) 
Metastases To Central Nervous System  1  1/779 (0.13%) 
Tumour Associated Fever  1  1/779 (0.13%) 
Nervous system disorders   
Dizziness  1  1/779 (0.13%) 
Encephalopathy  1  1/779 (0.13%) 
Generalised Tonic-Clonic Seizure  1  1/779 (0.13%) 
Headache  1  1/779 (0.13%) 
Paraparesis  1  1/779 (0.13%) 
Posterior Reversible Encephalopathy Syndrome  1  3/779 (0.39%) 
Subarachnoid Haemorrhage  1  1/779 (0.13%) 
White Matter Lesion  1  1/779 (0.13%) 
Product Issues   
Thrombosis In Device  1  1/779 (0.13%) 
Psychiatric disorders   
Confusional State  1  4/779 (0.51%) 
Renal and urinary disorders   
Acute Kidney Injury  1  3/779 (0.39%) 
Hydronephrosis  1  3/779 (0.39%) 
Nephrotic Syndrome  1  5/779 (0.64%) 
Prerenal Failure  1  1/779 (0.13%) 
Proteinuria  1  2/779 (0.26%) 
Urinary Retention  1  2/779 (0.26%) 
Respiratory, thoracic and mediastinal disorders   
Acute Pulmonary Oedema  1  2/779 (0.26%) 
Atelectasis  1  1/779 (0.13%) 
Cough  1  1/779 (0.13%) 
Dyspnoea  1  4/779 (0.51%) 
Haemoptysis  1  2/779 (0.26%) 
Hiccups  1  2/779 (0.26%) 
Pleural Effusion  1  2/779 (0.26%) 
Pneumonia Aspiration  1  1/779 (0.13%) 
Pneumonitis  1  1/779 (0.13%) 
Pneumothorax  1  1/779 (0.13%) 
Pulmonary Embolism  1  9/779 (1.16%) 
Pulmonary Haemorrhage  1  1/779 (0.13%) 
Respiratory Failure  1  2/779 (0.26%) 
Thoracic Haemorrhage  1  1/779 (0.13%) 
Surgical and medical procedures   
Cancer Surgery  1  2/779 (0.26%) 
Vascular disorders   
Deep Vein Thrombosis  1  4/779 (0.51%) 
Hypertension  1  11/779 (1.41%) 
Hypotension  1  2/779 (0.26%) 
Orthostatic Hypotension  1  1/779 (0.13%) 
Peripheral Ischaemia  1  1/779 (0.13%) 
Vena Cava Thrombosis  1  1/779 (0.13%) 
1
Term from vocabulary, MedDra 19.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Affected / at Risk (%)
Total   744/779 (95.51%) 
Blood and lymphatic system disorders   
Neutropenia  1  277/779 (35.56%) 
Gastrointestinal disorders   
Abdominal Pain  1  150/779 (19.26%) 
Abdominal Pain Upper  1  67/779 (8.60%) 
Constipation  1  148/779 (19.00%) 
Diarrhoea  1  464/779 (59.56%) 
Nausea  1  337/779 (43.26%) 
Proctalgia  1  39/779 (5.01%) 
Stomatitis  1  329/779 (42.23%) 
Vomiting  1  190/779 (24.39%) 
General disorders   
Asthenia  1  192/779 (24.65%) 
Fatigue  1  283/779 (36.33%) 
Pyrexia  1  87/779 (11.17%) 
Investigations   
Weight Decreased  1  171/779 (21.95%) 
Metabolism and nutrition disorders   
Decreased Appetite  1  206/779 (26.44%) 
Musculoskeletal and connective tissue disorders   
Back Pain  1  47/779 (6.03%) 
Nervous system disorders   
Headache  1  105/779 (13.48%) 
Psychiatric disorders   
Insomnia  1  54/779 (6.93%) 
Renal and urinary disorders   
Proteinuria  1  102/779 (13.09%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  57/779 (7.32%) 
Dysphonia  1  131/779 (16.82%) 
Dyspnoea  1  62/779 (7.96%) 
Epistaxis  1  153/779 (19.64%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  143/779 (18.36%) 
Palmar-Plantar Erythrodysaesthesia Syndrome  1  79/779 (10.14%) 
Vascular disorders   
Hypertension  1  369/779 (47.37%) 
1
Term from vocabulary, MedDra 19.0
Indicates events were collected by systematic assessment
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.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Trial Transparency Team
Organization: Sanofi
Phone: 800-633-1610 ext 1#
EMail: Contact-US@sanofi.com
Layout table for additonal information
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01571284     History of Changes
Other Study ID Numbers: AFLIBC06097
2011-005724-17
U1111-1125-8949 ( Other Identifier: UTN )
First Submitted: April 3, 2012
First Posted: April 5, 2012
Results First Submitted: January 29, 2018
Results First Posted: February 27, 2018
Last Update Posted: April 17, 2018