A Phase I-II Trial of Depsipeptide in Patients With Recurrent High-Grade Gliomas
I. Determine the maximum tolerated dose (MTD) of FR901228 (depsipeptide) in patients with
recurrent malignant gliomas who are taking enzyme-inducing antiepileptic drugs (EIAEDs).
(Phase I) II. Determine the safety profile of this drug in these patients. (Phase I) III.
Determine the pharmacokinetics and pharmacodynamics of this drug in these patients. (Phase
I) IV. Determine the clinical efficacy of this drug, as measured by 6-month progression-free
survival and objective tumor response, in these patients. (Phase II) V. Determine the
safety profile of this drug when administered at the phase I MTD concurrently with or
without EIAEDs in these patients. (Phase II)
OUTLINE: This is a multicenter, phase I, dose-escalation study followed by a phase II
study. Patients are stratified according to study phase (I vs II), concurrent use of
enzyme-inducing anti-epileptic drugs (EIAEDs) (yes vs no), histology (recurrent glioblastoma
multiforme/gliosarcoma vs recurrent anaplastic glioma), pre-operative candidacy (yes vs no),
and measurable/evaluable disease (yes vs no). Patients are assigned to 1 of 2 treatment
groups (group A: no EIAEDs or group B: concurrent use of EIAEDs).
Phase I (group B only): Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1,
8, and 15. Courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of FR901228 until
the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding
that at which 2 of up to 6 patients experience dose-limiting toxicity.
Phase II (groups A and B):
Group A (phase II): Patients receive FR901228 as in phase I at dose level 1. Group B (phase
II): Patients receive FR901228 as in phase I at the MTD.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of depsipeptide determined by dose-limiting toxicities graded according to the NCI Common Toxicity Criteria (CTCAE Version 3.0) (Phase I)
First 4 weeks of treatment
North American Brain Tumor Consortium
United States: Food and Drug Administration
|North American Brain Tumor Consortium||Watertown, Massachusetts 02472|