A Phase I Study of SU5416 in Pediatric Patients With Recurrent or Progressive Poor Prognosis 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.
Endpoint Classification: Safety Study, Primary Purpose: Treatment
Toxicities of SU5416 in children and adolescents with refractory CNS malignancies
Mark W. Kieran, MD, PhD
Dana-Farber Cancer Institute
United States: Food and Drug Administration
|Baylor College of Medicine||Houston, Texas 77030|
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Duke Comprehensive Cancer Center||Durham, North Carolina 27710|
|UCSF Cancer Center and Cancer Research Institute||San Francisco, California 94115-0128|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|Children's National Medical Center||Washington, District of Columbia 20010-2970|
|Children's Hospital of Pittsburgh||Pittsburgh, Pennsylvania 15213|
|Children's Hospital and Regional Medical Center - Seattle||Seattle, Washington 98105|
|Saint Jude Children's Research Hospital||Memphis, Tennessee 38105-2794|