A phase I/II trial of the histone deacetylase inhibitor romidepsin for adults with recurrent malignant glioma: North American brain tumor consortium study 03-03 Academic Article uri icon


MeSH Major

  • Antibiotics, Antineoplastic
  • Brain Neoplasms
  • Depsipeptides
  • Glioma
  • Histone Deacetylase Inhibitors
  • Neoplasm Recurrence, Local


  • Romidepsin, a potent histone deacetylase inhibitor, has shown activity in preclinical glioma models. The primary objectives of this trial were to determine the pharmacokinetics of romidepsin in patients with recurrent glioma on enzyme-inducing antiepileptic drugs (EIAEDs) and to evaluate the antitumor efficacy of romidepsin in patients with recurrent glioblastoma who were not receiving EIAEDs. Two dose cohorts were studied in the phase I component of the trial (13.3 and 17.7 mg/m(2)/d). Patients in the phase II component were treated with intravenous romidepsin at a dosage of 13.3 mg/m(2)/day on days 1, 8, and 15 of each 28-day cycle. Eight patients were treated on the phase I component. A similar romidepsin pharmacokinetic profile was demonstrated between patients receiving EIAEDs to those not receving EIAEDs. Thirty-five patients with glioblastoma were accrued to the phase II component. There was no objective radiographic response. The median progression-free survival (PFS) was 8 weeks and only 1 patient had a PFS time ≥6 months (PFS6 = 3%). To date, 34 patients (97%) have died, with a median survival duration of 34 weeks. Despite in vitro studies showing that romidepsin is primarily metabolized by CYP3A4, no decrease in exposure to romidepsin was seen in patients receiving potent CYP3A4 inducers. Romidepsin, at its standard dose and schedule, was ineffective for patients with recurrent glioblastomas. ClinicalTrials.gov identifier: NCT00085540.

publication date

  • May 2011



  • Academic Article



  • eng

PubMed Central ID

  • PMC3093337

Digital Object Identifier (DOI)

  • 10.1093/neuonc/nor017

PubMed ID

  • 21377994

Additional Document Info

start page

  • 509

end page

  • 16


  • 13


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