A Phase I/II Trial of SU5416 in Patients With Recurrent High Grade Astrocytomas or Mixed Gliomas
OBJECTIVES: Phase I:
- Determine the maximum tolerated dose of SU5416 in patients with recurrent malignant
glioma who are, as well as those who are not, taking enzyme-inducing antiepileptic
- Determine the toxic effects (safety profile) of this drug in this patient population.
- Characterize the pharmacokinetics of this drug in these patients.
- Develop exploratory data relative to surrogate endpoints of angiogenic activity in
vivo, including functional imaging and in vitro assays of endothelial cell inhibition
and serum angiogenic peptides.
- Determine the efficacy of SU5416, in terms of 6-month progression-free survival, in
patients with recurrent high-grade glioma.
- Determine, further, the safety profile of the phase II dose of this drug in this
- Develop exploratory data relative to surrogate endpoints of angiogenic activity in vivo
including functional imaging and in vitro assays of endothelial cell inhibition and
serum angiogenic peptides.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to
concurrent enzyme-inducing antiepileptic drugs (no vs yes).
Patients receive SU5416 IV on days 1 and 4 weekly for 4 weeks. Courses repeat every 4 weeks
in the absence of unacceptable toxicity or disease progression.
Cohorts of 3-6 patients receive escalating doses of SU5416 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6
patients experience dose-limiting toxicity. Once the MTD has been determined, additional
patients are accrued to the phase II portion of the study. These patients receive SU5416 IV,
as in the phase I portion, at the appropriate MTD established in phase I.
Patients are followed for survival.
PROJECTED ACCRUAL: At least 30 patients will be accrued for the phase I dose-escalation
portion of this study within 10 months. An additional 48 patients (32 with glioblastoma
multiforme and 16 with anaplastic glioma) will be accrued for the phase II portion of this
study within 6-8 months.
Primary Purpose: Treatment
Howard A. Fine, MD
NCI - Neuro-Oncology Branch
United States: Federal Government
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|
|University of Texas - MD Anderson Cancer Center||Houston, Texas 77030-4009|
|University of Michigan Comprehensive Cancer Center||Ann Arbor, Michigan 48109-0752|
|Jonsson Comprehensive Cancer Center, UCLA||Los Angeles, California 90095-1781|
|Simmons Cancer Center - Dallas||Dallas, Texas 75235-9154|
|University of Texas Health Science Center at San Antonio||San Antonio, Texas 78284-7811|
|UCSF Cancer Center and Cancer Research Institute||San Francisco, California 94115-0128|
|University of Pittsburgh Cancer Institute||Pittsburgh, Pennsylvania 15213|
|University of Wisconsin Comprehensive Cancer Center||Madison, Wisconsin 53792|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|Children's Hospital of Pittsburgh||Pittsburgh, Pennsylvania 15213|
|Neuro-Oncology Branch||Bethesda, Maryland 20892|