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

Neuro Oncol. 2011 May;13(5):509-16. doi: 10.1093/neuonc/nor017. Epub 2011 Mar 3.


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 types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Antibiotics, Antineoplastic / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Depsipeptides / pharmacokinetics
  • Depsipeptides / therapeutic use*
  • Female
  • Follow-Up Studies
  • Glioma / drug therapy*
  • Glioma / pathology
  • Histone Deacetylase Inhibitors / pharmacokinetics
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Survival Rate
  • Tissue Distribution
  • Treatment Outcome


  • Antibiotics, Antineoplastic
  • Depsipeptides
  • Histone Deacetylase Inhibitors
  • romidepsin

Associated data

  • ClinicalTrials.gov/NCT00085540