Back to resultsA Study of Aflibercept in Combination With FOLFIRI in Patients With Second-Line Metastatic Colorectal Cancer in Japan
Primary Purpose
Colorectal Cancer Metastatic
Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Aflibercept
Levofolinate
Irinotecan
5-FU
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer Metastatic
Eligibility Criteria
Inclusion criteria:
- Histologically or cytologically proven adenocarcinoma of the colon or rectum.
- Metastatic disease that was not amenable to potentially curative treatment.
- Participants with measurable disease.
- One prior chemotherapeutic regimen (containing oxaliplatin) for metastatic disease.
- Participants who relapsed within 6 months of completion of oxaliplatin-based adjuvant chemotherapy were also eligible.
Exclusion criteria:
- Prior therapy with irinotecan.
- Less than 28 days elapsed from prior radiotherapy, prior surgery, or prior chemotherapy to the time of registration.
- Unresolved toxicity (grade >1) from prior anticancer therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status >1.
- Brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis.
- Other prior malignancy.
- Pregnant or breast-feeding women.
- Uncontrolled hypertension.
- Inadequate bone marrow function, liver function, or renal function.
The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Sites / Locations
- Investigational Site Number 392011
- Investigational Site Number 392018
- Investigational Site Number 392016
- Investigational Site Number 392017
- Investigational Site Number 392001
- Investigational Site Number 392019
- Investigational Site Number 392015
- Investigational Site Number 392013
- Investigational Site Number 392004
- Investigational Site Number 392006
- Investigational Site Number 392014
- Investigational Site Number 392008
- Investigational Site Number 392003
- Investigational Site Number 392009
- Investigational Site Number 392012
- Investigational Site Number 392005
- Investigational Site Number 392002
- Investigational Site Number 392010
- Investigational Site Number 392007
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Aflibercept + FOLFIRI
Arm 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.
Outcomes
Primary Outcome Measures
Percentage of Participants With Overall Response
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.
Secondary Outcome Measures
Progression Free Survival (PFS)
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.
Overall Survival (OS)
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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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.
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
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.
Maximum Observed Plasma Concentration (Cmax) for Free Aflibercept: ITT Population
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.
Area Under the Concentration Time Curve From Time 0 to 14 Days Post Start of Infusion (AUC0-14 Day) for Free Aflibercept: ITT Population
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.
Area Under the Concentration Time Curve (AUC) for Free Aflibercept: ITT Population
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.
Total Body Clearance (CL) for Free Aflibercept: ITT Population
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.
Volume of Distribution at the Steady State (Vss) for Free Aflibercept: ITT Population
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.
Maximum Observed Plasma Concentration (Cmax) for Free and Vascular Endothelial Growth Factor (VEGF)-Bound Aflibercept: Participants With Additional Blood Sampling for Detailed PK Analysis
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 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
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.
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
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.
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
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.
Area Under the Concentration Time Curve (AUC) for Free Aflibercept: Participants With Additional Blood Sampling for Detailed PK Analysis
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.
Total Body Clearance (CL) for Free Aflibercept: Participants With Additional Blood Sampling for Detailed PK Analysis
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.
Volume of Distribution at the Steady State (Vss) for Free Aflibercept: Participants With Additional Blood Sampling for Detailed PK Analysis
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.
Terminal Elimination Half-life (t1/2z) for Free Aflibercept: Participants With Additional Blood Sampling for Detailed PK Analysis
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.
Steady State Drug Concentration (Css) for 5-FU: Participants With Additional Blood Sampling for Detailed PK Analysis
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.
Clearance at Steady State (CLss) for 5-FU: Participants With Additional Blood Sampling for Detailed PK Analysis
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.
Maximum Observed Plasma Concentration (Cmax) for Irinotecan and Its Active Metabolite SN-38: Participants With Additional Blood Sampling for Detailed PK Analysis
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.
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
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.
Area Under the Concentration Time Curve (AUC) for Irinotecan and Its Active Metabolite SN-38: Participants With Additional Blood Sampling for Detailed PK Analysis
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.
Terminal Elimination Half-life (t1/2z) for Irinotecan and Its Active Metabolite SN-38: Participants With Additional Blood Sampling for Detailed PK Analysis
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.
Active Metabolite SN-38 / Irinotecan Ratio on Area Under the Concentration Time Curve (Rmet): Participants With Additional Blood Sampling for Detailed PK Analysis
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.
Total Body Clearance (CL) for Irinotecan: Participants With Additional Blood Sampling for Detailed PK Analysis
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.
Volume of Distribution at the Steady State (Vss) for Irinotecan: Participants With Additional Blood Sampling for Detailed PK Analysis
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.
Full Information
NCT ID
NCT01882868
First Posted
June 18, 2013
Last Updated
January 24, 2017
Sponsor
Sanofi
Collaborators
Regeneron Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01882868
Brief Title
A Study of Aflibercept in Combination With FOLFIRI in Patients With Second-Line Metastatic Colorectal Cancer in Japan
Official Title
A Single-Arm Phase II Study in Japan to Assess the Efficacy and Safety of Aflibercept Administered Every Two Weeks in Combination With FOLFIRI in Patients With Metastatic Colorectal Cancer Who Progressed During or Following an Oxaliplatin-Based Regimen
Study Type
Interventional
2. Study Status
Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
July 2013 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
August 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
Collaborators
Regeneron Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Primary Objective:
To assess efficacy aflibercept + 5-fluorouracil (5-FU)/levofolinate/irinotecan (FOLFIRI) by objective response rate (ORR).
Secondary Objective:
To assess the following:
safety profile;
progression free survival (PFS);
overall survival (OS);
pharmacokinetics (PK);
immunogenicity.
Detailed Description
Screening was up to 24 days. Treatment period was continued until DP, unacceptable toxicity, or participant's refusal. Follow up period was continued until death, participant's refusal, or end of study, whichever came first.
This trial was conducted in Japan, where the International Nonproprietary Name (INN) designation for the study molecule is "aflibercept" and this term is therefore used throughout the synopsis. In the US, the US proper name is "ziv-aflibercept".
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer Metastatic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
62 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Aflibercept + FOLFIRI
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Aflibercept
Other Intervention Name(s)
AVE0005
Intervention Description
Pharmaceutical form: Concentrated solution (100 mg/4 mL [25 mg/mL], 200 mg/8 mL [25 mg/mL]) for infusion; Route of administration: Intravenous
Intervention Type
Drug
Intervention Name(s)
Levofolinate
Intervention Description
Pharmaceutical form: Solution for infusion (marketed formulation); Route of administration: Intravenous
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Intervention Description
Pharmaceutical form: Solution for infusion (marketed formulation); Route of administration: Intravenous
Intervention Type
Drug
Intervention Name(s)
5-FU
Intervention Description
Pharmaceutical form: Solution for infusion (marketed formulation); Route of administration: Intravenous
Primary Outcome Measure Information:
Title
Percentage of Participants With Overall Response
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)
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
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)
Title
Overall Survival (OS)
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)
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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)
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
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
Title
Maximum Observed Plasma Concentration (Cmax) for Free Aflibercept: ITT Population
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
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
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
Title
Area Under the Concentration Time Curve (AUC) for Free Aflibercept: ITT Population
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
Title
Total Body Clearance (CL) for Free Aflibercept: ITT Population
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
Title
Volume of Distribution at the Steady State (Vss) for Free Aflibercept: ITT Population
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
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
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
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
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
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
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
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
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
Title
Area Under the Concentration Time Curve (AUC) for Free Aflibercept: Participants With Additional Blood Sampling for Detailed PK Analysis
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
Title
Total Body Clearance (CL) for Free Aflibercept: Participants With Additional Blood Sampling for Detailed PK Analysis
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
Title
Volume of Distribution at the Steady State (Vss) for Free Aflibercept: Participants With Additional Blood Sampling for Detailed PK Analysis
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
Title
Terminal Elimination Half-life (t1/2z) for Free Aflibercept: Participants With Additional Blood Sampling for Detailed PK Analysis
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
Title
Steady State Drug Concentration (Css) for 5-FU: Participants With Additional Blood Sampling for Detailed PK Analysis
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
Title
Clearance at Steady State (CLss) for 5-FU: Participants With Additional Blood Sampling for Detailed PK Analysis
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
Title
Maximum Observed Plasma Concentration (Cmax) for Irinotecan and Its Active Metabolite SN-38: Participants With Additional Blood Sampling for Detailed PK Analysis
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
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
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
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
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
Title
Terminal Elimination Half-life (t1/2z) for Irinotecan and Its Active Metabolite SN-38: Participants With Additional Blood Sampling for Detailed PK Analysis
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
Title
Active Metabolite SN-38 / Irinotecan Ratio on Area Under the Concentration Time Curve (Rmet): Participants With Additional Blood Sampling for Detailed PK Analysis
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
Title
Total Body Clearance (CL) for Irinotecan: Participants With Additional Blood Sampling for Detailed PK Analysis
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
Title
Volume of Distribution at the Steady State (Vss) for Irinotecan: Participants With Additional Blood Sampling for Detailed PK Analysis
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Histologically or cytologically proven adenocarcinoma of the colon or rectum.
Metastatic disease that was not amenable to potentially curative treatment.
Participants with measurable disease.
One prior chemotherapeutic regimen (containing oxaliplatin) for metastatic disease.
Participants who relapsed within 6 months of completion of oxaliplatin-based adjuvant chemotherapy were also eligible.
Exclusion criteria:
Prior therapy with irinotecan.
Less than 28 days elapsed from prior radiotherapy, prior surgery, or prior chemotherapy to the time of registration.
Unresolved toxicity (grade >1) from prior anticancer therapy.
Eastern Cooperative Oncology Group (ECOG) performance status >1.
Brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis.
Other prior malignancy.
Pregnant or breast-feeding women.
Uncontrolled hypertension.
Inadequate bone marrow function, liver function, or renal function.
The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 392011
City
Chiba-Shi
Country
Japan
Facility Name
Investigational Site Number 392018
City
Chuo-Ku
Country
Japan
Facility Name
Investigational Site Number 392016
City
Fukuoka-Shi
Country
Japan
Facility Name
Investigational Site Number 392017
City
Fukuoka-Shi
Country
Japan
Facility Name
Investigational Site Number 392001
City
Kashiwa-Shi
Country
Japan
Facility Name
Investigational Site Number 392019
City
Kawasaki-Shi
Country
Japan
Facility Name
Investigational Site Number 392015
City
Matsuyama-Shi
Country
Japan
Facility Name
Investigational Site Number 392013
City
Mitaka-Shi
Country
Japan
Facility Name
Investigational Site Number 392004
City
Nagoya-Shi
Country
Japan
Facility Name
Investigational Site Number 392006
City
Osaka-Shi
Country
Japan
Facility Name
Investigational Site Number 392014
City
Sagamihara-Shi
Country
Japan
Facility Name
Investigational Site Number 392008
City
Sapporo-Shi
Country
Japan
Facility Name
Investigational Site Number 392003
City
Sendai-Shi
Country
Japan
Facility Name
Investigational Site Number 392009
City
Shimotsuke-Shi
Country
Japan
Facility Name
Investigational Site Number 392012
City
Shinjuku-Ku
Country
Japan
Facility Name
Investigational Site Number 392005
City
Suita-Shi
Country
Japan
Facility Name
Investigational Site Number 392002
City
Sunto-Gun
Country
Japan
Facility Name
Investigational Site Number 392010
City
Tsukuba-Shi
Country
Japan
Facility Name
Investigational Site Number 392007
City
Yufu-Shi
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
31520559
Citation
Hamaguchi T, Denda T, Kudo T, Sugimoto N, Ura T, Yamazaki K, Fujii H, Kajiwara T, Nakajima TE, Takahashi S, Otsu S, Komatsu Y, Nagashima F, Moriwaki T, Esaki T, Sato T, Itabashi M, Oki E, Sasaki T, Chiron M, Yoshino T. Exploration of potential prognostic biomarkers in aflibercept plus FOLFIRI in Japanese patients with metastatic colorectal cancer. Cancer Sci. 2019 Nov;110(11):3565-3572. doi: 10.1111/cas.14198. Epub 2019 Oct 21.
Results Reference
derived
PubMed Identifier
30657223
Citation
Denda T, Sakai D, Hamaguchi T, Sugimoto N, Ura T, Yamazaki K, Fujii H, Kajiwara T, Nakajima TE, Takahashi S, Otsu S, Komatsu Y, Nagashima F, Moriwaki T, Esaki T, Sato T, Itabashi M, Oki E, Sasaki T, Sunaga Y, Ziti-Ljajic S, Brillac C, Yoshino T. Phase II trial of aflibercept with FOLFIRI as a second-line treatment for Japanese patients with metastatic colorectal cancer. Cancer Sci. 2019 Mar;110(3):1032-1043. doi: 10.1111/cas.13943. Epub 2019 Feb 22.
Results Reference
derived
Learn more about this trial
A Study of Aflibercept in Combination With FOLFIRI in Patients With Second-Line Metastatic Colorectal Cancer in Japan
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