Phase 2
Completed N=62
A Study of Aflibercept in Combination With FOLFIRI in Patients With Second-Line Metastatic Colorectal Cancer in Japan
Colorectal Cancer Metastatic
Source: ClinicalTrials.gov NCT01882868 ↗
Enrolled (actual)
62
Serious AEs
32.3%
Results posted
Mar 2017
Primary outcomePrimary: Percentage of Participants With Overall Response — 8.3 percentage of participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Overall Response |
8.3 | — |
| SECONDARY Progression Free Survival (PFS) |
5.42 | — |
| SECONDARY Overall Survival (OS) |
15.59 | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) |
62 | — |
| SECONDARY 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 |
1; 0; 0; 0; 0 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) for Free Aflibercept: ITT Population |
73.19 | — |
| SECONDARY Area Under the Concentration Time Curve From Time 0 to 14 Days Post Start of Infusion (AUC0-14 Day) for Free Aflibercept: ITT Population |
246.9 | — |
| SECONDARY Area Under the Concentration Time Curve (AUC) for Free Aflibercept: ITT Population |
304.6 | — |
| SECONDARY Total Body Clearance (CL) for Free Aflibercept: ITT Population |
0.8053 | — |
| SECONDARY Volume of Distribution at the Steady State (Vss) for Free Aflibercept: ITT Population |
6.197 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) for Free and Vascular Endothelial Growth Factor (VEGF)-Bound Aflibercept: Participants With Additional Blood Sampling for Detailed PK Analysis |
90.8; 2.83 | — |
| SECONDARY 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 |
0.07; 13.97 | — |
| SECONDARY 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 |
321; 24.4 | — |
| SECONDARY 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 |
312; 23.3 | — |
| SECONDARY Area Under the Concentration Time Curve (AUC) for Free Aflibercept: Participants With Additional Blood Sampling for Detailed PK Analysis |
355 | — |
| SECONDARY Total Body Clearance (CL) for Free Aflibercept: Participants With Additional Blood Sampling for Detailed PK Analysis |
0.716 | — |
| SECONDARY Volume of Distribution at the Steady State (Vss) for Free Aflibercept: Participants With Additional Blood Sampling for Detailed PK Analysis |
3.53 | — |
| SECONDARY Terminal Elimination Half-life (t1/2z) for Free Aflibercept: Participants With Additional Blood Sampling for Detailed PK Analysis |
4.47 | — |
| SECONDARY Steady State Drug Concentration (Css) for 5-FU: Participants With Additional Blood Sampling for Detailed PK Analysis |
930 | — |
| SECONDARY Clearance at Steady State (CLss) for 5-FU: Participants With Additional Blood Sampling for Detailed PK Analysis |
122 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) for Irinotecan and Its Active Metabolite SN-38: Participants With Additional Blood Sampling for Detailed PK Analysis |
2220; 32.2 | — |
| SECONDARY 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 |
16900; 344 | — |
| SECONDARY Area Under the Concentration Time Curve (AUC) for Irinotecan and Its Active Metabolite SN-38: Participants With Additional Blood Sampling for Detailed PK Analysis |
17700; 341 | — |
| SECONDARY Terminal Elimination Half-life (t1/2z) for Irinotecan and Its Active Metabolite SN-38: Participants With Additional Blood Sampling for Detailed PK Analysis |
5.19; 10.3 | — |
| SECONDARY Active Metabolite SN-38 / Irinotecan Ratio on Area Under the Concentration Time Curve (Rmet): Participants With Additional Blood Sampling for Detailed PK Analysis |
0.0313 | — |
| SECONDARY Total Body Clearance (CL) for Irinotecan: Participants With Additional Blood Sampling for Detailed PK Analysis |
18.3 | — |
| SECONDARY Volume of Distribution at the Steady State (Vss) for Irinotecan: Participants With Additional Blood Sampling for Detailed PK Analysis |
92.5 | — |
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.
Data sourced from ClinicalTrials.gov (NCT01882868). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.