Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The purpose of this study was to determine the maximum-tolerated dose (MTD), pharmacokinetics and safety profile for two different dosing regimens of barasertib, a selective inhibitor of Aurora B Kinase. In this Phase I trial, patients with advanced solid malignancies were treated with escalating doses of barasertib, administered as either a 48-h continuous infusion or as two 2-h infusions on consecutive days, both every 14 days of a 28-day cycle. Thirty-five patients were treated. The MTDs were 150 mg as a 48-h continuous infusion and 220 mg administered as two 2-h infusions (110 mg/day, days 1, 2, 15 and 16), with neutropenia the dose-limiting toxicity (DLT) of each schedule. Common Terminology Criteria of Adverse Events (CTCAE) grade ≥ 3 neutropenia (with or without fever) occurred in 34 % of patients overall. Other adverse events, many of hematologic or gastrointestinal etiology, were of mild or moderate intensity. No objective tumor responses were observed, although stable disease was observed in 23 % of patients. Systemic exposure to barasertib-hQPA, the more active moiety to which barasertib is converted, was observed by 1 and 6 h into the 2-h and continuous infusion, respectively, and exhibited linear pharmacokinetics. In summary, barasertib was generally well tolerated, with neutropenia the most frequent and dose-limiting toxicity, irrespective of schedule. Future development of barasertib will depend on better definition of its therapeutic index. © 2012 Springer Science+Business Media, LLC.

Original publication

DOI

10.1007/s10637-012-9825-7

Type

Journal article

Journal

Investigational New Drugs

Publication Date

2012

Pages

1 - 11