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A phase 2 trial of verubulin for recurrent glioblastoma: a prospective study by the brain tumor investigational consortium (BTIC)

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Abstract

Treatment options are limited for recurrent glioblastoma (GBM). Verubulin is a microtubule destabilizer and vascular disrupting agent that achieve high brain concentration relative to plasma in animals. Adults with recurrent GBM who failed prior standard therapy were eligible. The primary endpoint was 1-month progression-free survival (PFS-1) for bevacizumab refractory (Group 2) and 6-month progression-free survival (PFS-6) for bevacizumab naïve patients (Group 1). Verubulin was administered at 3.3 mg/m2 as a 2-h intravenous infusion once weekly for 3 consecutive weeks in a 4-week cycle. The planned sample size was 34 subjects per cohort. 56 patients (37 men, 19 women) were enrolled, 31 in Group 1 and 25 in Group 2. The PFS-6 for Group 1 was 14 % and the PFS-1 for Group 2 was 20 %. Median survival from onset of treatment was 9.5 months in Group 1 and 3.4 months in Group 2. Best overall response was partial response (n = 3; 10 % in Group 1; n = 1; 4.2 % in Group 2) and stable disease (n = 7; 23 % in Group 1; n = 5; 21 % in Group 2). In Group 1, 38.7 % of patients experienced a serious adverse event; however only 3.2 % were potentially attributable to study drug. In Group 2, 44 % of patients experienced a serious adverse event although none were attributable to study drug. Accrual was terminated early for futility. Single agent verubulin, in this dose and schedule, is well tolerated, associated with moderate but tolerable toxicity but has limited activity in either bevacizumab naïve or refractory recurrent GBM.

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Acknowledgments

Xiaoyu Chai and Brenda Kurland for help with statistical analysis and the Fred Hutchinson Research Cancer Center Biostatistics Shared Resource (funding source P30 CA015704) and Alisa Clein for administrative assistance in the preparation of the manuscript. This study was sponsored by Myriad Inc.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Seattle Cancer Care Alliance, Fred Hutchinson Cancer Center, University of Washington, 825 Eastlake Ave E, MS: G4-940, Seattle, WA, 98109, USA

    Marc C. Chamberlain

  2. Department of Neurology, Northwestern University, 710 N Lake Shore Drive, Abbott Hall, Room 1110, Chicago, IL, 60611, USA

    Sean Grimm

  3. Cedars Sinai Medical Center, 8631 W 3rd St, Ste 410-E, Los Angeles, CA, 90048, USA

    Surasak Phuphanich

  4. Stanford University, 875 Blake Wilbur Dr Rm 2221, Palo Alto, CA, 943042205, USA

    Larry Recht

  5. Tufts University, 750 Washington St, # 833, Boston, MA, 02111, USA

    Jay Z. Zhu

  6. Jefferson University, 900 Walnut Street, Suite 200, Philadelphia, PA, 19107, USA

    Lyndon Kim

  7. Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, 9500 Euclid Avenue, Mailcode: NB40, Cleveland, OH, 44195, USA

    Steve Rosenfeld

  8. Hematology/Oncology Section, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, 03756, USA

    Camilo E. Fadul

Authors
  1. Marc C. Chamberlain
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  2. Sean Grimm
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  3. Surasak Phuphanich
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  5. Jay Z. Zhu
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  7. Steve Rosenfeld
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  8. Camilo E. Fadul
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Brain Tumor Investigational Consortium (BTIC)

Corresponding author

Correspondence to Marc C. Chamberlain.

Additional information

ClinicalTrials.gov Identifier: NCT00892931.

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Chamberlain, M.C., Grimm, S., Phuphanich, S. et al. A phase 2 trial of verubulin for recurrent glioblastoma: a prospective study by the brain tumor investigational consortium (BTIC). J Neurooncol 118, 335–343 (2014). https://doi.org/10.1007/s11060-014-1437-y

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  • DOI: https://doi.org/10.1007/s11060-014-1437-y

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