PMID- 25529193
OWN - NLM
STAT- MEDLINE
DCOM- 20160119
LR  - 20211203
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Print)
IS  - 0167-6997 (Linking)
VI  - 33
IP  - 2
DP  - 2015 Apr
TI  - A phase 1 dose escalation study of BI 831266, an inhibitor of Aurora kinase B, in 
      patients with advanced solid tumors.
PG  - 409-22
LID - 10.1007/s10637-014-0201-7 [doi]
AB  - 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.
FAU - Dittrich, Christian
AU  - Dittrich C
AD  - Ludwig Boltzmann Institute for Applied Cancer Research (LBI-ACR VIEnna) - LB 
      Cluster Translational Oncology and Applied Cancer Research-Institution for 
      Translational Research Vienna (ACR-ITR VIEnna), Third Medical Department, Center 
      for Oncology and Hematology, Kaiser-Franz-Josef-Spital, Vienna, Austria, 
      christian.dittrich@wienkav.at.
FAU - Fridrik, Michael A
AU  - Fridrik MA
FAU - Koenigsberg, Robert
AU  - Koenigsberg R
FAU - Lee, Chooi
AU  - Lee C
FAU - Goeldner, Rainer-Georg
AU  - Goeldner RG
FAU - Hilbert, James
AU  - Hilbert J
FAU - Greil, Richard
AU  - Greil R
LA  - eng
SI  - EudraCT/2008-001631-36
SI  - ClinicalTrials.gov/NCT00756223
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20141223
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.11.1 (Aurora Kinase B)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/administration & dosage/adverse 
      effects/pharmacokinetics/*pharmacology
MH  - Aurora Kinase B/*antagonists & inhibitors
MH  - Disease-Free Survival
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasms/*drug therapy
MH  - Protein Kinase Inhibitors/administration & dosage/adverse 
      effects/pharmacokinetics/*pharmacology
MH  - Protein Serine-Threonine Kinases/administration & dosage/adverse 
      effects/pharmacokinetics/*pharmacology
PMC - PMC4387274
EDAT- 2014/12/23 06:00
MHDA- 2016/01/20 06:00
PMCR- 2014/12/23
CRDT- 2014/12/23 06:00
PHST- 2014/07/10 00:00 [received]
PHST- 2014/12/12 00:00 [accepted]
PHST- 2014/12/23 06:00 [entrez]
PHST- 2014/12/23 06:00 [pubmed]
PHST- 2016/01/20 06:00 [medline]
PHST- 2014/12/23 00:00 [pmc-release]
AID - 201 [pii]
AID - 10.1007/s10637-014-0201-7 [doi]
PST - ppublish
SO  - Invest New Drugs. 2015 Apr;33(2):409-22. doi: 10.1007/s10637-014-0201-7. Epub 
      2014 Dec 23.