Entry Detail
| General information | |
| Database: | DB00907 |
| Objective: | Foretinib is an oral multikinase inhibitor targeting Met, RON, Axl, and vascular endothelial growth factor receptor. they conducted a phase I, firsttimeinhuman, clinical trial using escalating doses of oral foretinib. The primary objectives are to identify a maximum tolerated dose and determine the safety profile of foretinib. evaluation of plasma pharmacokinetics, longterm safety after repeated administration, preliminary antitumor activity, and pharmacodynamic activity. |
| Authors: | Eder JP, et al |
| Title: | a phase I study of foretinib, a multitargeted inhibitor of cMet and vascular endothelial growth factor receptor 2. |
| Journal: | Clin Cancer Res. |
| Year: | 2010 |
| PMID: | 20472683 |
| Trial Design | |
| Clinical Trial Id: | NCT00742131 |
| Agent: | foretinib |
| Target: | Vascular endothelial growth factor receptor 2 Hepatocyte growth factor receptor |
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase I study |
| Key Patients Feature: | Patients had histologically confirmed metastatic or unresectable solid tumors for which no standard measures exist. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | All patients received foretinib orally for 5 consecutive days every 14 days. Dose escalation follotheyd a conventional "3+3" design. |
| Primary End Point: | a maximum tolerated dose and determine the safety profile of foretinib. |
| Secondary End Point: | plasma pharmacokinetics, longterm safety after repeated administration, preliminary antitumor activity, and pharmacodynamic activity. |
| Patients Number: | 40 |
| Trial Results | |
| DLT_MTD: | The maximum tolerated dose was defined as 3.6 mg/kg, with a maximum administered dose of 4.5 mg/kg. Doselimiting toxicities included grade 3 elevations in aspartate aminotransferase and lipase.Additional nondoselimiting adverse events included hypertension, fatigue, diarrhea, vomiting, proteinuria, and hematuria. |
| Objective Response Rate: | 7.50% |
| Disease Control Rate: | 62.50% |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Thirtynine (98%) patients reported at least one adverse event. Hypertension was an expected and frequently reported treatmentrelated adverse event (16 events in 12 patients).Hypertension was most often grade 1 or 2, with one grade 3 event at 1.6 mg/kg and two at 3.6 mg/kg. Elevations in AST occurred in 10 patients (25%), and all but one event were less than grade 3. Proteinuria was common, all grade 1 or 2, and resolved spontaneously in all but three of nine patients. |
| Conclusions: | The recommended dose of foretinib was determined to be 240 mg, given on the first 5 days of a 14day cycle. This dose and schedule were identified as having acceptable safety and pharmacokinetics, and will be the dose used in subsequentphase II trials. |