A Phase I Study of Sunitinib (SU11248), an Oral Multi-Targeted Tyrosine Kinase Inhibitor, in Children With Refractory Solid Tumors
I. Determine the maximum tolerated dose (MTD) and recommended phase II dose of sunitinib
malate in pediatric patients with refractory solid tumors.
II. Determine the toxicity of this regimen in these patients. III. Characterize the
pharmacokinetics of this regimen in these patients. IV. Evaluate the tolerability and
pharmacokinetic profile of sunitinib malate capsule contents sprinkled over applesauce or
yogurt using the recommended phase II dose.
I. Determine, preliminarily, the antitumor effects of this regimen in these patients.
II. Describe changes in peripheral blood monocyte counts, circulating endothelial cells, and
plasma angiogenic factors during treatment with sunitinib malate.
III. Explore changes in tumor vascular permeability using dynamic contrast-enhanced
(DCE)-magnetic resonance imaging (MRI) in patients receiving sunitinib malate.
OUTLINE: This is a multicenter, dose-escalation study (part A) followed by a
pediatric-friendly formulation study (part B).
PART A: Patients receive oral sunitinib malate once daily on days 1-28 days. Treatment
repeats every 42 days for up to 18 courses in the absence of disease progression or
Cohorts of 3-6 patients receive escalating doses of sunitinib malate until the 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.
PART B: Patients receive sunitinib malate capsule contents sprinkled over applesauce or
yogurt once daily on days 1-28. Treatment repeats every 42 days for up to 18 courses in the
absence of disease progression or unacceptable toxicity. After the first course, patients
may switch to capsule formulation for convenience.
NOTE: Patients will not receive sunitinib malate on day 2 of the first course to allow for
Blood is collected on days 1, 7, 14, 21, and 28 of course 1 for pharmacokinetic studies
using liquid chromatography/mass spectrometry.
After completion of study treatment, patients are followed up for 30 days.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD and recommended phase II dose
MTD will be the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT).
During course 1 of therapy
Children's Oncology Group
United States: Food and Drug Administration
|Baylor College of Medicine||Houston, Texas 77030|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|University of Alabama at Birmingham||Birmingham, Alabama 35294-3300|
|University of Texas Southwestern Medical Center||Dallas, Texas|
|Seattle Children's Hospital||Seattle, Washington 98105|
|University of California San Francisco Medical Center-Mount Zion||San Francisco, California 94115|
|Columbia University Medical Center||New York, New York 10032|
|University of California San Francisco Medical Center||San Francisco, California 94143|
|C S Mott Children's Hospital||Ann Arbor, Michigan 48109|