| General information |
| Database: | DB00713 |
| Objective: | Following the doseescalation stage, this doubleblind expansion stage of the phase I study evaluated the safety, pharmacodynamics, pharmacokinetics, antivascular effects and antitumour activity of aflibercept 4 mg/kg with irinotecan, 5fluorouracil and leucovorin (LV5FU2). |
| Authors: | Khayat D, et al |
| Title: | Intravenous aflibercept administered in combination with irinotecan, 5fluorouracil and leucovorin in patients with advanced solid tumours: results from the expansion cohort of a phase I study. |
| Journal: | Eur J Cancer. |
| Year: | 2013 |
| PMID: | 23312881 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | aflibercept
|
| Target: | Vascular endothelial growth factor receptor 2
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Intravenous aflibercept with irinotecan, 5fluorouracil and leucovorin |
| Study Type: | a doubleblind, multicentre, randomised, parallelgroup, placebocontrolled study |
| Key Patients Feature: | Key eligibility criteria included patients agedP18 years with histologically or cytologically confirmedsolid malignancy that was metastatic or unresectable orfor which no standard conventional therapy existed, butfor which treatment with irinotecan-LV5FU2 was considered appropriate; Eastern Cooperative OncologyGroup (ECOG) performance status 62; adequate organfunction; and resolution (grade 61) of any toxic manifestations (except for alopecia) from other anticancertreatments. Patients also had to have at least one measurable lesion amenable to DCEMRI. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | aflibercept VS placebo |
| Treatment Info: | Patients with advanced solid tumours were randomised at cycle1 to placebo or aflibercept (4 mg/kg) on day 1 then irinotecanLV5FU2 on days 1 and 2. Subsequently, all patients received aflibercept with irinotecanLV5FU2 every 2 weeks. Antivascular effects were assessed using dynamic contrastenhanced magnetic resonance imaging (DCEMRI). |
| Primary End Point: | safety and pharmacokinetics |
| Secondary End Point: | NA |
| Patients Number: | 27 |
| Trial Results |
| DLT_MTD: | Aflibercept 4 mg/kg plus irinotecanLV5FU2 every 2 weeks |
| Objective Response Rate: | Four patients achieved partial responses and 17 had stable disease, lasting >3 months in 14 patients. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Most frequent grade 3/4 adverse events were neutropenia (37%), fatigue (33%) and hypertension (30%). |
| Conclusions: | Aflibercept 4 mgkg plus irinotecanLV5FU2 every 2 weeks had acceptable toxicity and pharmacokinetics, and showed promising antitumour activity. |