An open-label, dose-escalation, safety, and pharmacokinetics phase I study of ombrabulin, a vascular disrupting agent, administered as a 30-min intravenous infusion every 3 weeks in Japanese patients with advanced solid tumors

PURPOSE: To determine ombrabulin’s maximum tolerated dose and dose recommended for Japanese patients with advanced solid tumors and to assess its antitumor activity and overall safety and pharmacokinetic profiles. METHODS: This was a multi-center, open-label, sequential-cohort, dose-escalation phase I study of ombrabulin, a vascular disrupting agent, administered once every 3 weeks. Patients were treated with 15.5, 25, 35, or 50 mg/m(2) ombrabulin over a 30-min intravenous infusion. The recommended dose was the highest dose at which <33 % of all evaluable patients experienced dose-limiting toxicities (DLTs) during the first treatment cycle or 50 mg/m(2) (recommended in Caucasian patients) if the previous definition was not met. RESULTS: Fifteen patients were treated. No DLT occurred with 15.5, 25, or 35 mg/m(2) ombrabulin. In the 50 mg/m(2) group, one patient had Grade 3 lymphopenia, and another experienced Grade 2 hypertension and Grade 3 diarrhea judged as DLTs. The most frequent related adverse events in this group were diarrhea, nausea, and hypertension. Two patients had Grade 3 anemia, one at the 15.5 mg/m(2) and the other at the 50 mg/m(2). No AEs necessitating dose reduction or Grade 4 AEs were observed. Overall, five patients had stable disease. Pharmacokinetic parameters were comparable to those in non-Japanese patients. CONCLUSIONS: Ombrabulin treatment once every 3 weeks was well tolerated in Japanese patients with advanced solid tumors. The dose recommended is 50 mg/m(2), as in Caucasian patients. The safety and pharmacokinetic profiles were comparable between Japanese and Caucasian patients (funded by Sanofi; ClinicalTrials.gov number, NCT00968916).