| Title |
A phase 1 dose escalation study of BI 831266, an inhibitor of Aurora kinase B, in patients with advanced solid tumors
|
|---|---|
| Published in |
Investigational New Drugs, December 2014
|
| DOI | 10.1007/s10637-014-0201-7 |
| Pubmed ID | |
| Authors |
Christian Dittrich, Michael A. Fridrik, Robert Koenigsberg, Chooi Lee, Rainer-Georg Goeldner, James Hilbert, Richard Greil |
| Abstract |
Purpose BI 831266 is a potent, selective, low-molecular-weight inhibitor of Aurora kinase B. This trial aimed to determine the maximum tolerated dose (MTD) of BI 831266 in patients with advanced solid tumors (NCT00756223; EudraCT 2008-001631-36; 1257.1). Methods BI 831266 (4-130 mg) was administered over 24 h on days 1 and 15 of a 4-week schedule. A modified 3 + 3 dose-escalation design was utilized to evaluate the MTD. Safety, pharmacokinetics, pharmacodynamics, objective response rate, progression-free survival (PFS) and exploratory biomarkers were secondary endpoints. Results Twenty-five patients received BI 831266. The most frequent tumor type was colorectal cancer (48 %). One patient (130 mg) experienced a dose-limiting toxicity of grade 3 febrile neutropenia. The trial was prematurely terminated (sponsor decision) without further dose-escalation. The most frequent treatment-related adverse events (AEs) were fatigue (20 %), neutropenia, alopecia (16 % each), anemia, dry skin, and nausea (12 % each). Treatment-related grade ≥3 AEs were neutropenia (12 %), anemia (8 %), and febrile neutropenia (4 %); 15 patients experienced serious AEs. High variability in the pharmacokinetic profiles precluded definitive pharmacokinetic conclusions. Exploratory biomarker determination revealed consistency with the mode of action as an Aurora kinase B inhibitor. One patient (4 %; 32 mg) with cervical cancer demonstrated a confirmed partial response (duration 141 days, PFS 414 days). Four patients had stable disease. Conclusion The MTD of BI 831266 was not reached because of early trial termination. BI 831266 demonstrated a generally manageable safety profile and signs of antitumor activity in some patients' solid tumors. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Germany | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 32 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 5 | 16% |
| Student > Ph. D. Student | 4 | 13% |
| Researcher | 3 | 9% |
| Lecturer | 2 | 6% |
| Student > Master | 1 | 3% |
| Other | 1 | 3% |
| Unknown | 16 | 50% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 6 | 19% |
| Biochemistry, Genetics and Molecular Biology | 3 | 9% |
| Agricultural and Biological Sciences | 3 | 9% |
| Business, Management and Accounting | 2 | 6% |
| Immunology and Microbiology | 1 | 3% |
| Other | 1 | 3% |
| Unknown | 16 | 50% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 December 2014.
All research outputs
#18,387,239
of 22,775,504 outputs
Outputs from Investigational New Drugs
#875
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Outputs of similar age
#255,548
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Outputs of similar age from Investigational New Drugs
#11
of 15 outputs
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