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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 2/2016

Open Access 01-08-2016 | Original Article

A phase I study of BI 811283, an Aurora B kinase inhibitor, in patients with advanced solid tumors

Authors: Klaus Mross, Heike Richly, Annette Frost, Dirk Scharr, Bahar Nokay, Ralph Graeser, Chooi Lee, James Hilbert, Rainer-George Goeldner, Oliver Fietz, Max E. Scheulen

Published in: Cancer Chemotherapy and Pharmacology | Issue 2/2016

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Abstract

Purpose

This phase I study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics, pharmacodynamics, and antitumor activity of the Aurora B kinase inhibitor BI 811283 in patients with advanced solid tumors.

Methods

BI 811283 was administered via 24-h infusion on Days 1 and 15 of a 4-week cycle (schedule A) or Day 1 of a 3-week cycle (schedule B) in a modified 3 + 3 dose-escalation design. Pharmacodynamic assessments included immunohistochemistry for phosphorylated histone H3 (pHH3) on skin biopsies to determine Aurora B kinase inhibition and plasma concentrations of caspase-cleaved CK-18 (apoptosis marker).

Results

A total of 121 patients were treated. The MTDs of BI 811283 were 125 mg (schedule A) and 230 mg (schedule B). Dose-limiting toxicities were primarily hematological (febrile neutropenia and grade 4 neutropenia); the most common drug-related adverse effects included neutropenia, fatigue, leukopenia, nausea, alopecia, diarrhea, and decreased appetite. A trend toward a decrease in pHH3 was observed, with increasing BI 811283 doses, indicating target engagement; there was no consistent trend regarding caspase-cleaved CK-18 levels. No objective response was observed although 19 patients in each schedule achieved clinical benefit (stable disease).

Conclusions

BI 811283 demonstrated a generally manageable safety profile and disease stabilization in some patients.

Trial registration

EudraCT No: 2007-000191-17, ClinicalTrials.gov Identifier: NCT00701324.
Appendix
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Metadata
Title
A phase I study of BI 811283, an Aurora B kinase inhibitor, in patients with advanced solid tumors
Authors
Klaus Mross
Heike Richly
Annette Frost
Dirk Scharr
Bahar Nokay
Ralph Graeser
Chooi Lee
James Hilbert
Rainer-George Goeldner
Oliver Fietz
Max E. Scheulen
Publication date
01-08-2016
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 2/2016
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-016-3095-6

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