RATIONALE: SU5416 may stop the growth of brain cancer cells by stopping blood flow to the tumor. PURPOSE: Phase I trial to study the safety of delivering SU5416 in children who have recurrent or progressive brain tumors.
OBJECTIVES: I. Determine the qualitative and quantitative toxicity of SU5416 in pediatric patients with recurrent or progressive brain tumors. II. Determine the acute and chronic dose-limiting toxicity and cumulative toxicity of this regimen in these patients. III. Determine the maximum tolerated dose and pharmacokinetics of this regimen in this patient population. IV. Determine the effects of hepatic enzyme-inducing drugs, such as anticonvulsant agents, on the pharmacokinetics of this regimen in these patients. V. Determine the efficacy, in a preliminary manner, of this regimen in these patients. OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to concurrent use of enzyme-inducing anticonvulsant drugs (yes vs no drugs or modest-induction drugs). Patients receive SU5416 IV over 1 hour twice a week for 6 weeks. Treatment repeats every 6 weeks for 17 courses (approximately 2 years) in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients in each stratum 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. Patients are followed every 3 months for 1 year, every 6 months for 4 years, and then annually for 5 years. PROJECTED ACCRUAL: A total of 50 patients (25 per stratum) will be accrued for this study.
Study Type
INTERVENTIONAL
Purpose
TREATMENT
Enrollment
33
UCSF Cancer Center and Cancer Research Institute
San Francisco, California, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Toxicities of SU5416 in children and adolescents with refractory CNS malignancies
Dose limiting toxicities of SU5416 in children and adolescents receiving enzyme inducing anticonvulsant drugs and in those not receiving enzyme inducing anticonvulsant drugs
Time frame: Six weeks
Pharmacokinetics of SU5416 and the effects of enzyme inducing anticonvulsant drugs on the pharmacokinetics
Tumor response to SU5416
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