| General information |
| Database: | DB00039 |
| Objective: | Thisphase I study cohort investigated aflibercept in combination with docetaxel in patients with advanced solid tumors |
| Authors: | Isambert N, et al |
| Title: | Phase I doseescalation study of intravenous aflibercept in combination with docetaxel in patients with advanced solid tumors. |
| Journal: | Clin Cancer Res. |
| Year: | 2012 |
| PMID: | 22261804 |
| Trial Design |
| Clinical Trial Id: | TCD6120 |
| Agent: | aflibercept
|
| Target: | VEGFA, vascular endothelial growth factor B, PIGF
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | aflibercept +docetaxel |
| Study Type: | a phase I doseescalation study |
| Key Patients Feature: | Eligible patients had metastatic or nonresectable cancer for which docetaxel was considered appropriate. (mean age, 56 y) Most had prior chemotherapy (96%) and most (24.1%) had breast cancer. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Patients received intravenous aflibercept (either 2, 4, 5, 6, 7, or 9 mg/kg) with docetaxel (75 mg/m(2)) on day 1 every 3 weeks until disease progression or unacceptable toxicity. |
| Primary End Point: | doselimiting toxicities (DLT) during cycle 1 and to determine the aflibercept recommendedphase II trial dose (RP2D) for combination with docetaxel. Pharmacokinetics, tolerability, and antitumor activity were also investigated. |
| Secondary End Point: | NA |
| Patients Number: | 54 |
| Trial Results |
| DLT_MTD: | In the doseescalationphase (n = 34), there were three DLTs: grade 4 neutropenic infection (2 mg/kg), grade 3 dysphonia (7 mg/kg), and grade 2 hypertension (9 mg/kg). An excess of freeoverbound aflibercept was observed at doses of 5 mg/kg or more. Aflibercept (6 mg/kg) was defined as the RP2D. |
| Objective Response Rate: | Seven patients had partial responses |
| Disease Control Rate: | Seven patients had partial responses, and 32 patients had stable disease (>3 months in 18 patients). |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most frequent grade 3/4 adverse events (AE) were neutropenia (85.2%), leukopenia (74.1%), hypertension (18.5%), and stomatitis (16.7%). AEs associated with vascular endothelial growth factor blockade included epistaxis (all grades, 83.3%), proteinuria (68.5%), dysphonia (68.5%), and hypertension (53.7%). |
| Conclusions: | On the basis of findings from this study, aflibercept (6 mgkg) was the dose recommended for further clinical development. |