Journal of Neuro-Oncology

, Volume 105, Issue 2, pp 375–381

Phase I and pharmacokinetic study of COL-3 in patients with recurrent high-grade gliomas

  • Michelle A. Rudek
  • Pamela New
  • Tom Mikkelsen
  • Surasak Phuphanich
  • Jane B. Alavi
  • Louis B. Nabors
  • Steven Piantadosi
  • Joy D. Fisher
  • Stuart A. Grossman
Clinical Study - Patient Study

DOI: 10.1007/s11060-011-0602-9

Cite this article as:
Rudek, M.A., New, P., Mikkelsen, T. et al. J Neurooncol (2011) 105: 375. doi:10.1007/s11060-011-0602-9

Abstract

COL-3 is a chemically modified tetracycline that targets multiple aspects of matrix metalloproteinase regulation. This phase I clinical trial was conducted to determine the maximum tolerated dose (MTD) of COL-3 in adults with recurrent high-grade glioma, to describe the effects of enzyme-inducing antiseizure drugs (EIADs) on its pharmacokinetics, and to obtain preliminary evidence of activity. Adults with recurrent high-grade glioma were stratified by EIAD use. COL-3 was given orally daily without interruption until disease progression or treatment-related dose-limiting toxicity (DLT). Three patients in each EIAD group were evaluated at each dose level beginning with 25 mg/m2/day and escalated by 25 mg/m2/day. Toxicity, response, and pharmacokinetics were assessed. Thirty-three patients were evaluated. The MTD was 75 mg/m2/day in the −EIAD patients while one was not determined in +EIAD patients. The common toxicities observed were anemia, ataxia, diarrhea, hypokalemia, CNS hemorrhage, and myalgia. One partial response was observed. −EIAD patients tended to have a higher steady-state trough concentration that was apparent only at the 100 mg/m2/day dose level (P = 0.01). This study suggests that: (a) EIAD use does affect the pharmacokinetics of COL-3 at higher doses; and (b) there was not enough suggestion of single-agent activity to warrant further study in recurrent high-grade gliomas.

Keywords

COL-3AnticonvulsantsPharmacokineticsGliomas

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Michelle A. Rudek
    • 2
  • Pamela New
    • 1
  • Tom Mikkelsen
    • 3
  • Surasak Phuphanich
    • 4
    • 7
  • Jane B. Alavi
    • 5
  • Louis B. Nabors
    • 6
  • Steven Piantadosi
    • 2
    • 7
  • Joy D. Fisher
    • 2
  • Stuart A. Grossman
    • 2
    • 8
  1. 1.Department of NeurosurgeryBaylor College of MedicineHoustonUSA
  2. 2.Department of OncologyThe Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimoreUSA
  3. 3.Department of NeurosurgeryHenry Ford HospitalDetroitUSA
  4. 4.Department of Hematology-Oncology, Winship Cancer InstituteEmory UniversityAtlantaUSA
  5. 5.Department of Hematology/OncologyHospital of the University of PennsylvaniaPhiladelphiaUSA
  6. 6.Department of NeurologyUniversity of AlabamaBirminghamUSA
  7. 7.Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical CenterLos AngelesUSA
  8. 8.NABTT Central OfficeJohns Hopkins UniversityBaltimoreUSA