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

Research output: Contribution to journalArticle

18 Citations (Scopus)

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/m 2 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.

Original languageEnglish (US)
Pages (from-to)257-264
Number of pages8
JournalJournal of neuro-oncology
Volume110
Issue number2
DOIs
StatePublished - Jan 1 2012

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Carboplatin
Glioblastoma
Disease-Free Survival
verubulin
Maximum Tolerated Dose
Hypesthesia
Cerebral Hemorrhage
Brain Ischemia
Heterografts
Microtubules
Thrombocytopenia
Area Under Curve
Blood Vessels
Half-Life
Anemia
Survival Rate
Safety
Recurrence

All Science Journal Classification (ASJC) codes

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

Grossmann, K. F., Colman, H., Akerley, W. A., Glantz, M., Matsuoko, Y., Beelen, A. P., ... Jensen, R. L. (2012). Phase i trial of verubulin (MPC-6827) plus carboplatin in patients with relapsed glioblastoma multiforme. Journal of neuro-oncology, 110(2), 257-264. https://doi.org/10.1007/s11060-012-0964-7
Grossmann, Kenneth F. ; Colman, Howard ; Akerley, Wallace A. ; Glantz, Michael ; Matsuoko, Yuko ; Beelen, Andrew P. ; Yu, Margaret ; De Groot, John F. ; Aiken, Robert D. ; Olsen, Jeffery J. ; Evans, Brent A. ; Jensen, Randy L. / Phase i trial of verubulin (MPC-6827) plus carboplatin in patients with relapsed glioblastoma multiforme. In: Journal of neuro-oncology. 2012 ; Vol. 110, No. 2. pp. 257-264.
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Grossmann, KF, Colman, H, Akerley, WA, Glantz, M, Matsuoko, Y, Beelen, AP, Yu, M, De Groot, JF, Aiken, RD, Olsen, JJ, Evans, BA & Jensen, RL 2012, 'Phase i trial of verubulin (MPC-6827) plus carboplatin in patients with relapsed glioblastoma multiforme', Journal of neuro-oncology, vol. 110, no. 2, pp. 257-264. https://doi.org/10.1007/s11060-012-0964-7

Phase i trial of verubulin (MPC-6827) plus carboplatin in patients with relapsed glioblastoma multiforme. / Grossmann, Kenneth F.; Colman, Howard; Akerley, Wallace A.; Glantz, Michael; Matsuoko, Yuko; Beelen, Andrew P.; Yu, Margaret; De Groot, John F.; Aiken, Robert D.; Olsen, Jeffery J.; Evans, Brent A.; Jensen, Randy L.

In: Journal of neuro-oncology, Vol. 110, No. 2, 01.01.2012, p. 257-264.

Research output: Contribution to journalArticle

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T1 - Phase i trial of verubulin (MPC-6827) plus carboplatin in patients with relapsed glioblastoma multiforme

AU - Grossmann, Kenneth F.

AU - Colman, Howard

AU - Akerley, Wallace A.

AU - Glantz, Michael

AU - Matsuoko, Yuko

AU - Beelen, Andrew P.

AU - Yu, Margaret

AU - De Groot, John F.

AU - Aiken, Robert D.

AU - Olsen, Jeffery J.

AU - Evans, Brent A.

AU - Jensen, Randy L.

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