Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01670721 | Colorectal Cancer Metastatic | PHASE3 | COMPLETED | 175 | — | — | Aug 1, 2012 | Jun 1, 2015 | Nov 28, 2016 | 1 | France |
| NCT01661270 | A Study of Aflibercept Versus Placebo With FOLFIRI in Patients With Metastatic Colorectal Cancer Previously Treated With an Oxaliplatin Chemotherapy | PHASE3 | COMPLETED | 332 | — | — | Jul 1, 2012 | Jul 1, 2015 | Oct 18, 2016 | 37 | China, Hong Kong +3 |
| NCT01882868 | A Study of Aflibercept in Combination With FOLFIRI in Patients With Second-Line Metastatic Colorectal Cancer in Japan | PHASE2 | COMPLETED | 62 | — | — | Jul 1, 2013 | Aug 1, 2015 | Mar 14, 2017 | 19 | Japan |
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.
PFS was defined as the time interval from the date of randomization to the date of first observation of either tumor progression or death due to any cause. Tumor assessment was performed by Independent Review Committee (IRC) as per response evaluation criteria in solid tumors (RECIST) version 1.0. Progression was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study or absolute increase and at least 5 mm, progression of existing non-target lesions, or presence of new lesions. PFS was calculated by Kaplan-Meier estimates.
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.
| Arm | Type | Description |
|---|---|---|
| Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin) | EXPERIMENTAL | 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. |
| Placebo | PLACEBO_COMPARATOR | Placebo for aflibercept intravenous (IV) infusion on Day 1 of each cycle (1 cycle = 2 weeks) in combination with FOLFIRI regimen until disease progression, unacceptable toxicity or participant's refusal. FOLFIRI regimen: Irinotecan 180 mg/m\^2 IV infusion and leucovorin 400 mg/m\^2 IV infusion, 5-Fluorouracil IV bolus 400 mg/m\^2 followed by continuous IV infusion 2400 mg/m\^2. |
| Aflibercept | EXPERIMENTAL | Aflibercept 4 mg/kg IV infusion on Day 1 of each cycle (1 cycle = 2 weeks) in combination with FOLFIRI regimen until disease progression, unacceptable toxicity or participant's refusal. FOLFIRI regimen: Irinotecan 180 mg/m\^2 IV infusion and leucovorin 400 mg/m\^2 IV infusion, 5-Fluorouracil IV bolus 400 mg/m\^2 followed by continuous IV infusion 2400 mg/m\^2. |
| Aflibercept + FOLFIRI | EXPERIMENTAL | 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. |
| Name | Type | Description |
|---|---|---|
| AFLIBERCEPT | DRUG | Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous |
| Irinotecan | DRUG | Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous |
| Fluorouracil | DRUG | Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous |
| Leucovorin | DRUG | Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous |
| Placebo | DRUG | Pharmaceutical form: Concentrate for Solution for infusion; Route of administration: Intravenous |
| Levofolinate | DRUG | Pharmaceutical form: Solution for infusion (marketed formulation); Route of administration: Intravenous |
| 5-FU | DRUG | Pharmaceutical form: Solution for infusion (marketed formulation); Route of administration: Intravenous |
Inclusion criteria: * Histologically or cytologically proven adenocarcinoma of the colon or rectum. * Metastatic disease. * Age ≥18 years. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1. * One and only one prior chemotherapeutic regimen for metastatic disease. This prior ch...