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A Study of Aflibercept in Combination With FOLFIRI in Patients With Second-Line Metastatic Colorectal Cancer in Japan

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ClinicalTrials.gov Identifier: NCT01882868
Recruitment Status : Completed
First Posted : June 20, 2013
Results First Posted : March 14, 2017
Last Update Posted : March 14, 2017
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
Drug: Levofolinate
Drug: Irinotecan
Drug: 5-FU
Enrollment 62
Recruitment Details The study was conducted at 19 sites in Japan. A total of 68 participants were screened between 30 July 2013 and 12 March 2014, out of which 62 were enrolled and treated.
Pre-assignment Details Among 68 participants screened, 6 were screen failures due to elevated urine protein-creatinine ratio (UPCR) and inadequate liver function tests (LFTs).
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description Aflibercept 4 mg/kg intravenous (IV) infusion (1-2 hours) on Day 1 of Cycle 1 and every 2 weeks (q2w) thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until disease progression (DP), unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Period Title: Overall Study
Started 62
Completed 62
Not Completed 0
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Baseline Participants 60
Hide Baseline Analysis Population Description
Evaluable participant (EP) population: all registered participants with measurable disease at study entry & with at least 1 valid post-baseline tumor evaluation. Participants who died due to DP or had documented radiological progressive disease before first post-baseline imaging evaluation were also included.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 60 participants
61.6  (9.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 60 participants
Female
26
  43.3%
Male
34
  56.7%
Eastern Cooperative Oncology Group Performance Status (ECOG PS)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 60 participants
0 40
1 20
[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.
Prior Treatment with Bevacizumab  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 60 participants
Had Prior Treatment 50
Did Not Have Prior Treatment 10
1.Primary Outcome
Title Percentage of Participants With Overall Response
Hide Description Overall response in participants was defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) assessed by an independent radiological review committee (IRRC) according to response evaluation criteria in solid tumors (RECIST) version 1.1. CR was defined as disappearance of all target lesions; any lymph node (target or non-target) must have reduction in the short axis to <10 mm; PR was defined as at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Percentage of participants with overall response and the 95% confidence interval (CI) were provided. The 95% CI was calculated using normal approximation.
Time Frame Baseline and every 6 weeks until DP (maximum duration: 16.4 months)
Hide Outcome Measure Data
Hide Analysis Population Description
EP population: all registered participants with measurable disease at study entry & with at least 1 valid post-baseline tumor evaluation. Participants who died due to DP or had documented radiological progressive disease before first post-baseline imaging evaluation were also included.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 60
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
8.3
(1.3 to 15.3)
2.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS was defined as the time interval from the date of first study drug administration to the date of first observation of DP or death due to any cause, whichever came first. If death or progression was not observed, the participant was censored at the date of participant’s last valid progression-free tumor assessment prior to the study cut-off date. DP for PFS was assessed by the IRRC based on tumor imaging according to RECIST 1.1. Progression in disease was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study with absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. PFS was estimated by Kaplan-Meier estimates.
Time Frame Baseline and every 6 weeks until DP or death, due to any cause (maximum duration: 16.4 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population (all treated [AT] population) included all registered participants who received at least 1 (even if incomplete) infusion of study treatment.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 62
Median (95% Confidence Interval)
Unit of Measure: months
5.42
(4.140 to 6.702)
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time interval from the date of first study drug administration to the date of death due to any cause. If death was not observed, the participant was censored at the last date the participant was known to be alive or the study cut-off date, whichever was first. OS was estimated by Kaplan-Meier estimates.
Time Frame Baseline up to death or study cut­-off (maximum duration: 24.7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population (AT population) included all registered participants who received at least 1 (even if incomplete) infusion of study treatment.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 62
Median (95% Confidence Interval)
Unit of Measure: months
15.59
(11.203 to 19.811)
4.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Hide Description Adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened during the on-­treatment period which was defined as the period from the time of first dose of study treatment until 30 days after the last dose of study treatment.
Time Frame First dose (Day 1 of Cycle 1) of study treatment up to end of treatment visit (30 days after last dose of study treatment) (maximum duration: 77 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population (AT population) included all registered participants who received at least 1 (even if incomplete) infusion of study treatment.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 62
Measure Type: Number
Unit of Measure: participants
62
5.Secondary Outcome
Title Aflibercept Immunogenicity Assessment: Number of Participants With Positive Sample(s) in the Anti-drug Antibodies (ADA) Assay and in the Neutralizing Anti-drug Antibodies (NAb) Assay
Hide Description Blood samples of participants were analyzed by using a titer-based, bridging immunoassay developed and validated to detect aflibercept ADA in human serum. Samples with positive antibody levels were further analyzed using a validated, non-quantitative, competitive ligand binding assay to detect NAb.
Time Frame Baseline, at any time post baseline and 90 days after the last dose of aflibercept
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population (AT population) included all registered participants who received at least 1 (even if incomplete) infusion of study treatment. Here 'n' signifies number of participants with available data for specified category.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 62
Measure Type: Number
Unit of Measure: participants
At baseline in the ADA assay (n=62) 1
At any time post-baseline in the ADA assay (n=62) 0
At any time post-baseline in the NAb assay (n=62) 0
At 90 days after last dose in the ADA assay (n=50) 0
At 90 days after last dose in NAb assay (n=50) 0
6.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) for Free Aflibercept: ITT Population
Hide Description Sparse blood sampling was performed on 52 participants and additional blood sampling for detailed pharmacokinetic (PK) analysis was performed on 10 participants as per protocol. A population PK analysis was performed and an overall data is reported for all the participants.
Time Frame Pre-dose, 1, 4, 24, 336 hours post aflibercept infusion on Day 1 of Cycle 1 for participants with sparse sampling & pre-dose, 1, 2, 4, 8, 24, 48, 168, 336 hours post aflibercept infusion on Day 1 of Cycle 1 for participants with additional sampling
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) population included all registered participants.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 62
Mean (Standard Deviation)
Unit of Measure: mcg/mL
73.19  (10.72)
7.Secondary Outcome
Title Area Under the Concentration Time Curve From Time 0 to 14 Days Post Start of Infusion (AUC0-14 Day) for Free Aflibercept: ITT Population
Hide Description Sparse blood sampling was performed on 52 participants and additional blood sampling for detailed PK analysis was performed on 10 participants as per protocol. A population PK analysis was performed and an overall data is reported for all the participants.
Time Frame Pre-dose, 1, 4, 24, 336 hours post aflibercept infusion on Day 1 of Cycle 1 for participants with sparse sampling & pre-dose, 1, 2, 4, 8, 24, 48, 168, 336 hours post aflibercept infusion on Day 1 of Cycle 1 for participants with additional sampling
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all registered participants.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 62
Mean (Standard Deviation)
Unit of Measure: mcg*day/mL
246.9  (41.1)
8.Secondary Outcome
Title Area Under the Concentration Time Curve (AUC) for Free Aflibercept: ITT Population
Hide Description Sparse blood sampling was performed on 52 participants and additional blood sampling for detailed PK analysis was performed on 10 participants as per protocol. A population PK analysis was performed and an overall data is reported for all the participants.
Time Frame Pre-dose, 1, 4, 24, 336 hours post aflibercept infusion on Day 1 of Cycle 1 for participants with sparse sampling & pre-dose, 1, 2, 4, 8, 24, 48, 168, 336 hours post aflibercept infusion on Day 1 of Cycle 1 for participants with additional sampling
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all registered participants.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 62
Mean (Standard Deviation)
Unit of Measure: mcg*day/mL
304.6  (62.8)
9.Secondary Outcome
Title Total Body Clearance (CL) for Free Aflibercept: ITT Population
Hide Description Sparse blood sampling was performed on 52 participants and additional blood sampling for detailed PK analysis was performed on 10 participants as per protocol. A population PK analysis was performed and an overall data is reported for all the participants.
Time Frame Pre-dose, 1, 4, 24, 336 hours post aflibercept infusion on Day 1 of Cycle 1 for participants with sparse sampling & pre-dose, 1, 2, 4, 8, 24, 48, 168, 336 hours post aflibercept infusion on Day 1 of Cycle 1 for participants with additional sampling
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all registered participants.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 62
Mean (Standard Deviation)
Unit of Measure: liter/day
0.8053  (0.1784)
10.Secondary Outcome
Title Volume of Distribution at the Steady State (Vss) for Free Aflibercept: ITT Population
Hide Description Sparse blood sampling was performed on 52 participants and additional blood sampling for detailed PK analysis was performed on 10 participants as per protocol. A population PK analysis was performed and an overall data is reported for all the participants.
Time Frame Pre-dose, 1, 4, 24, 336 hours post aflibercept infusion on Day 1 of Cycle 1 for participants with sparse sampling & pre-dose, 1, 2, 4, 8, 24, 48, 168, 336 hours post aflibercept infusion on Day 1 of Cycle 1 for participants with additional sampling
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all registered participants.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 62
Mean (Standard Deviation)
Unit of Measure: liters
6.197  (1.106)
11.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) for Free and Vascular Endothelial Growth Factor (VEGF)-Bound Aflibercept: Participants With Additional Blood Sampling for Detailed PK Analysis
Hide Description In 10 participants of ITT population, additional blood samples were obtained for detailed non-compartmental PK analysis of free and VEGF-bound aflibercept in combination with irinotecan and 5-FU in Cycle 1.
Time Frame Predose (prior to aflibercept infusion), 1, 2, 4, 8, 24, 48, 168 and 336 hours post aflibercept infusion on Day 1 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Subset of ITT population with additional blood sampling for detailed non-compartmental PK analysis. Number of participants analyzed=participants with PK assessment for the subset analysis. Here 'n' signifies number of participants with available data for specified category.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: mcg/mL
Plasma Free-Aflibercept (n=10) 90.8  (16.5)
Plasma VEGF-Bound Aflibercept (n=8) 2.83  (0.836)
12.Secondary Outcome
Title Time to Reach Maximum Plasma Concentration Observed (Tmax) for Free and VEGF-Bound Aflibercept in Cycle 1: Participants With Additional Blood Sampling for Detailed PK Analysis
Hide Description In 10 participants of ITT population, additional blood samples were obtained for detailed non-compartmental PK analysis of free and VEGF-bound aflibercept in combination with irinotecan and 5-FU in Cycle 1.
Time Frame Predose (prior to aflibercept infusion), 1, 2, 4, 8, 24, 48, 168 and 336 hours post aflibercept infusion on Day 1 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Subset of ITT population with additional blood sampling for detailed non-compartmental PK analysis. Number of participants analyzed=participants with PK assessment for the subset analysis. Here 'n' signifies number of participants with available data for specified category.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 10
Median (Full Range)
Unit of Measure: days
Plasma Free-Aflibercept (n=10)
0.07
(0.04 to 0.09)
Plasma VEGF-Bound Aflibercept (n=8)
13.97
(7.01 to 16.05)
13.Secondary Outcome
Title Area Under the Concentration Time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Free and VEGF-Bound Aflibercept: Participants With Additional Blood Sampling for Detailed PK Analysis
Hide Description In 10 participants of ITT population, additional blood samples were obtained for detailed non-compartmental PK analysis of free and VEGF-bound aflibercept in combination with irinotecan and 5-FU in Cycle 1.
Time Frame Predose (prior to aflibercept infusion), 1, 2, 4, 8, 24, 48, 168 and 336 hours post aflibercept infusion on Day 1 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Subset of ITT population with additional blood sampling for detailed non-compartmental PK analysis. Number of participants analyzed=participants with PK assessment for the subset analysis. Here 'n' signifies number of participants with available data for specified category.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: mcg*day/mL
Plasma Free-Aflibercept (n=10) 321  (58.9)
Plasma VEGF-Bound Aflibercept (n=8) 24.4  (6.17)
14.Secondary Outcome
Title Area Under the Concentration Time Curve From Time 0 to 14 Days Post Start of Infusion (AUC0-14 Day) for Free and VEGF-Bound Aflibercept: Participants With Additional Blood Sampling for Detailed PK Analysis
Hide Description In 10 participants of ITT population, additional blood samples were obtained for detailed non-compartmental PK analysis of free and VEGF-bound aflibercept in combination with irinotecan and 5-FU in Cycle 1.
Time Frame Predose (prior to aflibercept infusion), 1, 2, 4, 8, 24, 48, 168 and 336 hours post aflibercept infusion on Day 1 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Subset of ITT population with additional blood sampling for detailed non-compartmental PK analysis. Number of participants analyzed=participants with PK assessment for the subset analysis. Here 'n' signifies number of participants with available data for specified category.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: mcg*day/mL
Plasma Free-Aflibercept (n=10) 312  (51.8)
Plasma VEGF-Bound Aflibercept (n=5) 23.3  (2.45)
15.Secondary Outcome
Title Area Under the Concentration Time Curve (AUC) for Free Aflibercept: Participants With Additional Blood Sampling for Detailed PK Analysis
Hide Description In 10 participants of ITT population, additional blood samples were obtained for detailed non-compartmental PK analysis of free aflibercept in combination with irinotecan and 5-FU in Cycle 1.
Time Frame Pre-dose (prior to aflibercept infusion), 1, 2, 4, 8, 24, 48, 168 and 336 hours post aflibercept infusion on Day 1 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Subset of ITT population with additional blood sampling for detailed non-compartmental PK analysis. Number of participants analyzed=participants with PK assessment for the subset analysis.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: mcg*day/mL
355  (61.5)
16.Secondary Outcome
Title Total Body Clearance (CL) for Free Aflibercept: Participants With Additional Blood Sampling for Detailed PK Analysis
Hide Description In 10 participants of ITT population, additional blood samples were obtained for detailed non-compartmental PK analysis of free aflibercept in combination with irinotecan and 5-FU in Cycle 1.
Time Frame Pre-dose (prior to aflibercept infusion), 1, 2, 4, 8, 24, 48, 168 and 336 hours post aflibercept infusion on Day 1 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Subset of ITT population with additional blood sampling for detailed non-compartmental PK analysis. Number of participants analyzed=participants with PK assessment for the subset analysis.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: liter/day
0.716  (0.204)
17.Secondary Outcome
Title Volume of Distribution at the Steady State (Vss) for Free Aflibercept: Participants With Additional Blood Sampling for Detailed PK Analysis
Hide Description In 10 participants of ITT population, additional blood samples were obtained for detailed non-compartmental PK analysis of free aflibercept in combination with irinotecan and 5-FU in Cycle 1.
Time Frame Pre-dose (prior to aflibercept infusion), 1, 2, 4, 8, 24, 48, 168 and 336 hours post aflibercept infusion on Day 1 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Subset of ITT population with additional blood sampling for detailed non-compartmental PK analysis. Number of participants analyzed=participants with PK assessment for the subset analysis.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: liters
3.53  (1.11)
18.Secondary Outcome
Title Terminal Elimination Half-life (t1/2z) for Free Aflibercept: Participants With Additional Blood Sampling for Detailed PK Analysis
Hide Description In 10 participants of ITT population, additional blood samples were obtained for detailed non-compartmental PK analysis of free aflibercept in combination with irinotecan and 5-FU in Cycle 1.
Time Frame Pre-dose (prior to aflibercept infusion), 1, 2, 4, 8, 24, 48, 168 and 336 hours post aflibercept infusion on Day 1 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Subset of ITT population with additional blood sampling for detailed non-compartmental PK analysis. Number of participants analyzed=participants with PK assessment for the subset analysis.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: days
4.47  (0.680)
19.Secondary Outcome
Title Steady State Drug Concentration (Css) for 5-FU: Participants With Additional Blood Sampling for Detailed PK Analysis
Hide Description In 10 participants of ITT population, additional blood samples were obtained for detailed non-compartmental PK analysis of 5-FU in combination with aflibercept and irinotecan in Cycle 1.
Time Frame Pre-dose (prior to aflibercept infusion), 2.5, 21 and 45 hours post 5-FU infusion on Day 1 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Subset of ITT population with additional blood sampling for detailed non-compartmental PK analysis. Number of participants analyzed=participants with PK assessment for the subset analysis.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: ng/mL
930  (461)
20.Secondary Outcome
Title Clearance at Steady State (CLss) for 5-FU: Participants With Additional Blood Sampling for Detailed PK Analysis
Hide Description In 10 participants of ITT population, additional blood samples were obtained for detailed non-compartmental PK analysis of 5-FU in combination with aflibercept and irinotecan in Cycle 1.
Time Frame Pre-dose (prior to aflibercept infusion), 2.5, 21 and 45 hours post 5-FU infusion on Day 1 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Subset of ITT population with additional blood sampling for detailed non-compartmental PK analysis. Number of participants analyzed=participants with PK assessment for the subset analysis.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: liter/hour
122  (76.2)
21.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) for Irinotecan and Its Active Metabolite SN-38: Participants With Additional Blood Sampling for Detailed PK Analysis
Hide Description In 10 participants of ITT population, additional blood samples were obtained for detailed non-compartmental PK analysis of irinotecan and SN-38 in combination with aflibercept and 5-FU in Cycle 1.
Time Frame Predose (prior to aflibercept infusion), 1.5, 2, 4.5 and 23 hours post irinotecan infusion on Day 1 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Subset of ITT population with additional blood sampling for detailed non-compartmental PK analysis. Number of participants analyzed=participants with PK assessment for the subset analysis.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: ng/mL
Plasma Irinotecan 2220  (528)
Plasma SN-38 32.2  (11.4)
22.Secondary Outcome
Title Area Under the Concentration Time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Irinotecan and Its Active Metabolite SN-38: Participants With Additional Blood Sampling for Detailed PK Analysis
Hide Description In 10 participants of ITT population, additional blood samples were obtained for detailed non-compartmental PK analysis of irinotecan and SN-38 in combination with aflibercept and 5-FU in Cycle 1.
Time Frame Pre-dose (prior to aflibercept infusion), 1.5, 2, 4.5 and 23 hours post irinotecan infusion on Day 1 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Subset of ITT population with additional blood sampling for detailed non-compartmental PK analysis. Number of participants analyzed=participants with PK assessment for the subset analysis.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
Plasma Irinotecan 16900  (5970)
Plasma SN-38 344  (173)
23.Secondary Outcome
Title Area Under the Concentration Time Curve (AUC) for Irinotecan and Its Active Metabolite SN-38: Participants With Additional Blood Sampling for Detailed PK Analysis
Hide Description In 10 participants of ITT population, additional blood samples were obtained for detailed non-compartmental PK analysis of irinotecan and SN-38 in combination with aflibercept and 5-FU in Cycle 1.
Time Frame Pre-dose (prior to aflibercept infusion), 1.5, 2, 4.5 and 23 hours post irinotecan infusion on Day 1 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Subset of ITT population with additional blood sampling for detailed non-compartmental PK analysis. Number of participants analyzed=participants with PK assessment for the subset analysis. Here 'n' signifies number of participants with available data for specified category.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
Plasma Irinotecan (n=10) 17700  (6400)
Plasma SN-38 (n=4) 341  (72.4)
24.Secondary Outcome
Title Terminal Elimination Half-life (t1/2z) for Irinotecan and Its Active Metabolite SN-38: Participants With Additional Blood Sampling for Detailed PK Analysis
Hide Description In 10 participants of ITT population, additional blood samples were obtained for detailed non-compartmental PK analysis of irinotecan and SN-38 in combination with aflibercept and 5-FU in Cycle 1.
Time Frame Pre-dose (prior to aflibercept infusion), 1.5, 2, 4.5 and 23 hours post irinotecan infusion on Day 1 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Subset of ITT population with additional blood sampling for detailed non-compartmental PK analysis. Number of participants analyzed=participants with PK assessment for the subset analysis. Here 'n' signifies number of participants with available data for specified category.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: hours
Plasma Irinotecan (n=10) 5.19  (0.736)
Plasma SN-38 (n=5) 10.3  (3.08)
25.Secondary Outcome
Title Active Metabolite SN-38 / Irinotecan Ratio on Area Under the Concentration Time Curve (Rmet): Participants With Additional Blood Sampling for Detailed PK Analysis
Hide Description In 10 participants of ITT population, additional blood samples were obtained for detailed non - compartmental PK analysis of irinotecan and SN-38 in combination with aflibercept and 5-FU in Cycle 1.
Time Frame Pre-dose (prior to aflibercept infusion), 1.5, 2, 4.5 and 23 hours post irinotecan infusion on Day 1 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Subset of ITT population with additional blood sampling for detailed non-compartmental PK analysis. Number of participants analyzed=participants with PK assessment for the subset analysis. Here 'n' signifies number of participants with available data for specified category.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: ratio
0.0313  (0.0133)
26.Secondary Outcome
Title Total Body Clearance (CL) for Irinotecan: Participants With Additional Blood Sampling for Detailed PK Analysis
Hide Description In 10 participants of ITT population, additional blood samples were obtained for detailed non-compartmental PK analysis of irinotecan in combination with aflibercept and 5-FU in Cycle 1.
Time Frame Pre-dose (prior to aflibercept infusion), 1.5, 2, 4.5 and 23 hours post irinotecan infusion on Day 1 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Subset of ITT population with additional blood sampling for detailed non-compartmental PK analysis. Number of participants analyzed=participants with PK assessment for the subset analysis.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: liter/hour
18.3  (6.04)
27.Secondary Outcome
Title Volume of Distribution at the Steady State (Vss) for Irinotecan: Participants With Additional Blood Sampling for Detailed PK Analysis
Hide Description In 10 participants of ITT population, additional blood samples were obtained for detailed non-compartmental PK analysis of irinotecan in combination with aflibercept and 5-FU in Cycle 1.
Time Frame Predose (prior to aflibercept infusion), 1.5, 2, 4.5 and 23 hours post irinotecan infusion on Day 1 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Subset of ITT population with additional blood sampling for detailed non-compartmental PK analysis. Number of participants analyzed=participants with PK assessment for the subset analysis.
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description:
Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: liter
92.5  (33.8)
Time Frame All AEs were collected from signature of the informed consent form up to the final visit (77 weeks) regardless of seriousness or relationship to investigational medicinal product.
Adverse Event Reporting Description Reported AEs are TEAEs that is AEs that developed/worsened during the study treatment period (defined as the first study treatment administration to End-of-Treatment Visit [30 days of last infusion]).
 
Arm/Group Title Aflibercept + FOLFIRI
Hide Arm/Group Description Aflibercept 4 mg/kg IV infusion (1-2 hours) on Day 1 of Cycle 1 and q2w thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until DP, unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m^2 (2 hours) and irinotecan 180 mg/m^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m^2.
All-Cause Mortality
Aflibercept + FOLFIRI
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Aflibercept + FOLFIRI
Affected / at Risk (%)
Total   20/62 (32.26%) 
Blood and lymphatic system disorders   
Febrile neutropenia  1  1/62 (1.61%) 
Gastrointestinal disorders   
Diarrhoea  1  1/62 (1.61%) 
Ileus  1  4/62 (6.45%) 
Oesophagitis  1  1/62 (1.61%) 
General disorders   
Catheter site pain  1  1/62 (1.61%) 
Fatigue  1  1/62 (1.61%) 
Pyrexia  1  1/62 (1.61%) 
Hepatobiliary disorders   
Cholecystitis  1  1/62 (1.61%) 
Cholecystitis acute  1  1/62 (1.61%) 
Infections and infestations   
Biliary tract infection  1  1/62 (1.61%) 
Peritonitis  1  1/62 (1.61%) 
Pharyngitis  1  1/62 (1.61%) 
Skin infection  1  1/62 (1.61%) 
Urinary tract infection  1  1/62 (1.61%) 
Injury, poisoning and procedural complications   
Lumbar vertebral fracture  1  1/62 (1.61%) 
Metabolism and nutrition disorders   
Decreased appetite  1  4/62 (6.45%) 
Dehydration  1  3/62 (4.84%) 
Musculoskeletal and connective tissue disorders   
Muscular weakness  1  1/62 (1.61%) 
Osteonecrosis of jaw  1  1/62 (1.61%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Metastases to central nervous system  1  1/62 (1.61%) 
Nervous system disorders   
Hepatic encephalopathy  1  1/62 (1.61%) 
Reproductive system and breast disorders   
Female genital tract fistula  1  1/62 (1.61%) 
Respiratory, thoracic and mediastinal disorders   
Interstitial lung disease  1  1/62 (1.61%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Aflibercept + FOLFIRI
Affected / at Risk (%)
Total   62/62 (100.00%) 
Blood and lymphatic system disorders   
Febrile neutropenia  1  4/62 (6.45%) 
Neutropenia  1  46/62 (74.19%) 
Gastrointestinal disorders   
Abdominal pain  1  9/62 (14.52%) 
Constipation  1  10/62 (16.13%) 
Diarrhoea  1  42/62 (67.74%) 
Nausea  1  36/62 (58.06%) 
Stomatitis  1  29/62 (46.77%) 
Vomiting  1  17/62 (27.42%) 
General disorders   
Fatigue  1  38/62 (61.29%) 
Pyrexia  1  13/62 (20.97%) 
Infections and infestations   
Nasopharyngitis  1  6/62 (9.68%) 
Upper respiratory tract infection  1  4/62 (6.45%) 
Investigations   
Weight decreased  1  6/62 (9.68%) 
Metabolism and nutrition disorders   
Decreased appetite  1  46/62 (74.19%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  5/62 (8.06%) 
Nervous system disorders   
Dysgeusia  1  5/62 (8.06%) 
Headache  1  7/62 (11.29%) 
Psychiatric disorders   
Insomnia  1  6/62 (9.68%) 
Renal and urinary disorders   
Proteinuria  1  19/62 (30.65%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  7/62 (11.29%) 
Dysphonia  1  18/62 (29.03%) 
Epistaxis  1  25/62 (40.32%) 
Hiccups  1  7/62 (11.29%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  30/62 (48.39%) 
Palmar-plantar erythrodysaesthesia syndrome  1  8/62 (12.90%) 
Rash  1  7/62 (11.29%) 
Skin hyperpigmentation  1  6/62 (9.68%) 
Vascular disorders   
Hot flush  1  4/62 (6.45%) 
Hypertension  1  29/62 (46.77%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
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
Name/Title: Trial Transparency Team
Organization: Sanofi
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01882868     History of Changes
Other Study ID Numbers: EFC11885
U1111-1120-0173 ( Other Identifier: UTN )
First Submitted: June 18, 2013
First Posted: June 20, 2013
Results First Submitted: August 26, 2016
Results First Posted: March 14, 2017
Last Update Posted: March 14, 2017