An open-label dose-escalation study of BIBF 1120 in patients with relapsed or refractory multiple myeloma.

Kropff M, Kienast J, Bisping G, Berdel WE, Gaschler-Markefski B, Stopfer P, Stefanic M, Munzert G

Abstract

BACKGROUND: To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of BIBF 1120, a triple angiokinase inhibitor administered once-daily in patients with advanced multiple myeloma. PATIENTS AND METHODS: This Phase I study included 17 patients. Planned dose escalations of BIBF 1120 were 100, 200, 250 and 300 mg. Safety and pharmacokinetic (PK) assessments were performed. RESULTS: Two DLTs (200 and 250 mg) occurred due to increased gamma-glutamyltransferase levels (CTC grade 3). The 250 mg dose was well tolerated; no dose escalation beyond 250 mg was made. The most common adverse events included diarrhoea, nausea and vomiting. No detectable deviation from dose linear PKs was observed. Regarding tumour control, two patients had stable disease for > or = 4 months. CONCLUSION: BIBF 1120 was safe and well tolerated up to 250 mg/day. The MTD was not reached.