A Phase I/II Trial Of MGI114 For Treatment Of Patients With Recurrent Malignant Gliomas
- Determine the maximum tolerated dose (MTD) of irofulven alone or combined with
anticonvulsants known to be metabolized by cytochrome P450 in patients with progressive
or recurrent high-grade anaplastic astrocytoma, anaplastic oligodendroglioma, or
- Assess the pharmacokinetics of this drug on this schedule and determine the effects of
P450-inducing anticonvulsants on the pharmacokinetics in these patients.
- Determine the response rate of patients treated with this drug administered at the MTD.
- Determine the duration of progression-free survival and overall survival of patients
treated with this drug.
- Determine the toxic effects of this drug in these patients.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to
concurrent use of anticonvulsant drugs that induce cytochrome P450 (yes vs no drugs or
Patients receive irofulven IV over 30 minutes on days 1-4 or 1-5 (depending on
dose-escalation level). Courses repeat every 4 weeks in the absence of disease progression
or unacceptable toxicity.
Cohorts of 3-6 patients (per stratum) receive escalating doses of irofulven until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which at least 2 of 6 patients experience dose-limiting toxicity. Once the MTD is
determined, additional patients are accrued to receive treatment with irofulven at the
recommended phase II dose.
Patients are followed at 1 week and then every 2 months thereafter.
PROJECTED ACCRUAL: Approximately 18 patients (9 per stratum) will be accrued for the phase I
portion of the study. Approximately 17-35 patients will be accrued for the phase II portion
of the study within 6-12 months.
Primary Purpose: Treatment
Steven S. Rosenfeld, MD, PhD
University of Alabama at Birmingham
United States: Federal Government
|H. Lee Moffitt Cancer Center and Research Institute
|Tampa, Florida 33612
|Emory University Hospital - Atlanta
|Atlanta, Georgia 30322
|University of Texas Health Science Center at San Antonio
|San Antonio, Texas 78284-7811
|Abramson Cancer Center of the University of Pennsylvania
|Philadelphia, Pennsylvania 19104-4283
|Massachusetts General Hospital Cancer Center
|Boston, Massachusetts 02114
|University of Alabama at Birmingham Comprehensive Cancer Center
|Birmingham, Alabama 35294-3300
|Comprehensive Cancer Center at Wake Forest University
|Winston-Salem, North Carolina 27157-1082
|Henry Ford Hospital
|Detroit, Michigan 48202
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
|Baltimore, Maryland 21231-2410
|Cleveland Clinic Taussig Cancer Center
|Cleveland, Ohio 44195