Journal of Neuro-Oncology

, Volume 110, Issue 2, pp 257–264 | Cite as

Phase I trial of verubulin (MPC-6827) plus carboplatin in patients with relapsed glioblastoma multiforme

  • Kenneth F. Grossmann
  • Howard Colman
  • Wallace A. Akerley
  • Michael Glantz
  • Yuko Matsuoko
  • Andrew P. Beelen
  • Margaret Yu
  • John F. De Groot
  • Robert D. Aiken
  • Jeffery J. Olsen
  • Brent A. Evans
  • Randy L. Jensen
Clinical Study

Abstract

Verubulin (MPC-6827) is a microtubule-destabilizing agent that achieves high concentrations in the brain. Verubulin disrupts newly formed blood vessels in xenografts. We determined the safety and tolerability of verubulin administered in combination with carboplatin in patients with relapsed glioblastoma multiforme (GBM). Three pre-selected doses of verubulin were tested: 2.1, 2.7, and 3.3 mg/m2 in a standard “3+3” design. Verubulin was given every second week of a 6-week cycle in the 2.1 mg/m2 cohort or weekly for 3 weeks of a 4-week cycle in subsequent cohorts. Carboplatin was administered intravenously at an area under the curve (AUC) dosage 4 every 2 weeks for the 2.1 mg/m2 cohort or on day 1 of each 4-week cycle in subsequent cohorts. Nineteen patients with GBM in first or second relapse were enrolled. Four patients (21 %) experienced a grade 3 or greater verubulin- or carboplatin-related adverse event, including hypesthesia, cerebral ischemia, anemia, and thrombocytopenia. The mean plasma half life of verubulin was 3.2 h (SD = 0.82). Two patients achieved at least a partial response by Macdonald criteria. One of these patients remains progression free and off treatment more than 24 months beyond his initiation of verubulin. Five patients had stable disease. Median progression-free survival (PFS) across all patients was 8 weeks, and the 6-month PFS rate was 21 %. The combination of verubulin at the previously determined single-agent maximum tolerated dose of 3.3 mg/m2 with carboplatin in patients with recurrent/refractory GBM is safe and well tolerated. In this patient population with a highly vascularized tumor, no cerebral hemorrhage was observed.

Keywords

Glioblastoma multiforme Verubulin Carboplatin Vascular disrupting agent 

Notes

Acknowledgments

We thank Kristin Kraus, MS, for editorial assistance in preparing this paper. This project was funded by Myrexis Inc. (formerly Myriad Pharmaceuticals).

Conflict of interest

The authors declare that there is no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Kenneth F. Grossmann
    • 1
  • Howard Colman
    • 2
  • Wallace A. Akerley
    • 1
  • Michael Glantz
    • 3
  • Yuko Matsuoko
    • 2
  • Andrew P. Beelen
    • 4
  • Margaret Yu
    • 5
  • John F. De Groot
    • 6
  • Robert D. Aiken
    • 7
  • Jeffery J. Olsen
    • 8
  • Brent A. Evans
    • 9
  • Randy L. Jensen
    • 10
  1. 1.Division of OncologyHuntsman Cancer Institute, University of UtahSalt Lake CityUSA
  2. 2.Department of NeurosurgeryHuntsman Cancer Institute, University of UtahSalt Lake CityUSA
  3. 3.Department of NeurosurgeryPenn State College of Medicine Hershey Medical CenterHersheyUSA
  4. 4.Department of Clinical ResearchMyrexis, IncSalt Lake CityUSA
  5. 5.Janssen Research and DevelopmentLos AngelesUSA
  6. 6.Department of Neuro-OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  7. 7.Department of Neuroscience, Neurosurgery, Medical Oncology, Radiation Oncology, Division of Neurological OncologyRush University Medical CenterChicagoUSA
  8. 8.Translational Neuro-oncology Laboratory, Department of Neurological SurgeryThe Emory ClinicAtlantaUSA
  9. 9.Department of BiostatisticsMyrexis, IncSalt Lake CityUSA
  10. 10.Departments of Neurosurgery, Radiation Oncology, Oncological Sciences, Huntsman Cancer InstituteClinical Neuroscience Center, University of UtahSalt Lake CityUSA

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