A phase I/II trial of the histone deacetylase inhibitor @entity783 for adults with recurrent XXXX : North American Brain Tumor Consortium Study 03-03.

@entity1 @entity5322 @entity783 @entity11 @entity463
@entity783 , a potent histone deacetylase inhibitor, has shown activity in preclinical @entity11 models. The primary objectives of this trial were to determine the pharmacokinetics of @entity783 in @entity1 with recurrent @entity11 on enzyme-inducing antiepileptic drugs (EIAEDs) and to evaluate the antitumor efficacy of @entity783 in @entity1 with recurrent @entity463 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). @entity1 in the phase II component were treated with intravenous @entity783 at a dosage of 13.3 mg/m(2)/day on days 1, 8, and 15 of each 28-day cycle. Eight @entity1 were treated on the phase I component. A similar @entity783 pharmacokinetic profile was demonstrated between @entity1 receiving EIAEDs to those not receving EIAEDs. Thirty-five @entity1 with @entity463 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 @entity1 had a PFS time >= 6 months (PFS6 = 3%). To date, 34 @entity1 (97%) have died, with a median survival duration of 34 weeks. Despite in vitro studies showing that @entity783 is primarily metabolized by @entity5322 , no decrease in exposure to @entity783 was seen in @entity1 receiving potent @entity5322 inducers. @entity783 , at its standard dose and schedule, was ineffective for @entity1 with recurrent @entity463 . ClinicalTrials.gov identifier: NCT00085540.
