Investigational New Drugs

, Volume 26, Issue 3, pp 241–247

A phase I trial of CEP-701 + gemcitabine in patients with advanced adenocarcinoma of the pancreas

  • Emily Chan
  • Daniel Mulkerin
  • Mace Rothenberg
  • Kyle D. Holen
  • A. Craig Lockhart
  • James Thomas
  • Jordan Berlin
PHASE I STUDIES

DOI: 10.1007/s10637-008-9118-3

Cite this article as:
Chan, E., Mulkerin, D., Rothenberg, M. et al. Invest New Drugs (2008) 26: 241. doi:10.1007/s10637-008-9118-3

Summary

Introduction: Current standard therapy for advanced pancreas cancer includes the use of gemcitabine or a gemcitabine-based chemotherapy regimen. Based on pre-clinical data, the combination of CEP-701, an inhibitor of tyrosine kinases including Flt-3, TRK-A/B and JCK-2, with gemcitabine appeared promising. Methods: Two clinical sites were chosen for this phase I trial, one scheduled to start gemcitabine prior to CEP-701 and one scheduled to start CEP-701 prior to gemcitabine. Gemcitabine was given at a dose of 1,000 mg/m2 over 30 min each week for 3 weeks in a row followed by 1 week off. CEP 701 was taken orally twice daily at doses ranging from 20 mg bid to 40 mg bid. Pharmacokinetics of both drugs were determined to assess for any drug–drug interactions. Results: Eighteen patients were enrolled and 17 received at least one dose of study drug. Nine patients experienced serious adverse events, but only one patient’s toxicity was attributed as possibly secondary to study drug. No radiologic responses were seen. No significant pharmacokinetic interactions were observed between gemcitabine and CEP 701. The combination was well-tolerated, and the MTD was not reached in this study. Conclusions: No unexpected toxicities were seen for this combination. Although too few patients were enrolled to fully evaluate efficacy, there was not significant evidence for pursuing this combination further in pancreas cancer. The maximum tolerated dose of the combination was not determined secondary to the early termination of the study.

Keywords

CEP-701 Pancreatic cancer Phase I trial 

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Emily Chan
    • 1
  • Daniel Mulkerin
    • 2
  • Mace Rothenberg
    • 1
  • Kyle D. Holen
    • 2
  • A. Craig Lockhart
    • 1
  • James Thomas
    • 3
  • Jordan Berlin
    • 1
  1. 1.Department of Medicine, Division of Hematology and OncologyVanderbilt University Medical CenterNashvilleUSA
  2. 2.Department of Medicine, Division of Hematology and OncologyUniversity of WisconsinMadisonUSA
  3. 3.Department of Medicine, Division of Hematology and OncologyOhio State UniversityColumbusUSA

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