Colorectal Cancer Metastatic

Phase 3

Completed

Conditions: Colorectal Cancer Metastatic

Interventions: Drug: AFLIBERCEPT
Drug: Irinotecan
Drug: Fluorouracil
Drug: Leucovorin

Registration Number: NCT01670721

Lead Sponsor: Sanofi

Brief Summary: Primary Objective:

To evaluate the safety of aflibercept in participants with mCRC treated with irinotecan/5-Fluorouracil (5-FU) combination (FOLFIRI) after failure of an oxaliplatin-based regimen (participants similar to those evaluated in the VELOUR trial \[EFC10262, NCT00561470\]) according to side effects prevention and management guidelines.

Secondary Objective:

To document the Health-Related Quality of Life (HRQL) of aflibercept in this participant population.

Detailed Description: Each participant was treated until disease progression (DP), unacceptable toxicity, death, Investigator's decision or participant's refusal for further treatment (whichever come first). Participants were followed-up during treatment and for at least 30 days after its last study treatment (either Aflibercept or FOLFIRI) administration, up to a maximum of 6 months.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 175

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)	Leucovorin	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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)	Irinotecan	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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)	AFLIBERCEPT	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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)	Fluorouracil	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 DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Adverse Events (AEs)	Baseline upto 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure:723 days)	Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period. On-treatment period was defined as the time from the first dose of treatment to 30 days after the last dose of treatment (either Aflibercept or FOLFIRI). A serious adverse event (SAE) was defined as 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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in HRQL European-Quality of Life-5 Dimension Instrument-3 Levels (EQ-5D-3L) Index Score	Pre-dose at Baseline, Day 1 of every odd cycle; and at end of treatment (30 days after last study treatment) (maximum exposure: 99 weeks)	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.
Change From Baseline in HRQL EQ-5D-3L VAS Score	Pre-dose at Baseline, Day 1 of every odd cycle; and at end of treatment (30 days after last study treatment) (maximum exposure: 99 weeks)	EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state. Baseline corresponded to last evaluable assessment before treatment administration.
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)	Pre-dose at Baseline, Day 1 of every odd cycle; and at end of treatment (30 days after last study treatment) (maximum exposure: 99 weeks)	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.