A Phase I/II Trial of BMS-247550 for Treatment of Patients With Recurrent High-grade Gliomas
I. To determine the maximum tolerated dose of BMS-247550 when administered to adults with
recurrent malignant gliomas, receiving (Group A) or not receiving (Group B) anticonvulsants
known to be metabolized by the P450 hepatic enzyme complex.
II. To describe the pharmacokinetics of this route of administration, measuring BMS-247550,
and determine the effects of hepatic enzyme inducing drugs, such as anticonvulsants, on the
III. To determine the response rate of adult patients with recurrent glioma to BMS-247550
administered at the MTD.
IV. To describe the toxicity associated with this regimen in adult patients with recurrent
I. To determine the percent of patients with 6 month progression free survival, duration of
progression free survival and survival associated with this therapy in adult patients with
recurrent malignant gliomas.
OUTLINE: This is a phase I, dose-escalation, multicenter study followed by a phase II,
safety and efficacy, multicenter study. For phase I only, patients are stratified according
to cytochrome P450-inducing anticonvulsant use (yes vs no).
Phase I: Patients receive ixabepilone IV over 1 hour on days 1-5. Courses repeat every 3
weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3 patients receive escalating doses of ixabepilone until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2
of 3 patients experience dose-limiting toxicity.
Phase II: Once the MTD is determined, additional patients receive ixabepilone as above at
Patients are followed every 2 months.
PROJECTED ACCRUAL: A minimum of 10-15 patients will be accrued for the phase I portion of
this study. A total of 22-33 patients will be accrued for the phase II portion of this study
within 4-6 months.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of BMS-247550 in patients with recurrent or progressive malignant glioma (Phase I)
New Approaches to Brain Tumor Therapy Consortium
United States: Food and Drug Administration
|New Approaches to Brain Tumor Therapy Consortium||Baltimore, Maryland 21231-1000|