Short Communication

Cancer Chemotherapy and Pharmacology

, Volume 73, Issue 1, pp 213-217

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Results of a phase I, open-label, randomized, crossover study evaluating the effects of linifanib on QTc intervals in patients with solid tumors

  • Yi-Lin ChiuAffiliated withAbbVie, Inc. Email author 
  • , Patricia LoRussoAffiliated withWayne State University
  • , Balakrishna HosmaneAffiliated withAbbVie, Inc.
  • , Justin L. RickerAffiliated withAbbVie, Inc.
  • , Walid AwniAffiliated withAbbVie, Inc.
  • , Dawn M. CarlsonAffiliated withAbbVie, Inc.



Linifanib is a selective inhibitor of the vascular endothelial growth factor and platelet-derived growth factor family of tyrosine kinase inhibitors. The purpose of this high-precision QT study was to evaluate the effects of linifanib on cardiac repolarization in patients with advanced metastatic tumors.


Enrolled patients (n = 24) had measurable disease refractory to standard therapies, ECOG performance status of 0–1, and adequate organ function. Patients were randomized in a 2-sequence, 2-period crossover design. Serial ECG measurements and pharmacokinetic samples were collected for each crossover period. An intersection–union test was performed for time-matched baseline-adjusted QTcF intervals. An exposure–response analysis was explored to correlate the plasma concentration and QTcF.


The maximum 95 % upper confidence bound for the baseline-adjusted QTcF was 4.3 ms at hour 3 at the maximum tolerated linifanib dose of 0.25 mg/kg. Linifanib did not meet the regulatory threshold (10 ms) for QT prolongation. Exposure–response modeling showed that the QTcF change was not significant at the maximum plasma concentration.


Linifanib does not significantly affect cardiac repolarization in patients with advanced solid tumors.


Tyrosine kinase inhibitors QT ECG VEGF