This phase I trial is studying the side effects and best dose of sunitinib in treating young patients with refractory solid tumors. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth and by blocking blood flow to the tumor.
PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: 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 unacceptable toxicity. 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 pharmacokinetic testing. 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
35
University of Alabama at Birmingham
Birmingham, Alabama, United States
Childrens Hospital of Orange County
Orange, California, United States
UCSF-Mount Zion
San Francisco, California, United States
University of California San Francisco Medical Center-Parnassus
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
C S Mott Children's Hospital
Ann Arbor, Michigan, United States
Washington University School of Medicine
St Louis, Missouri, United States
Columbia University Medical Center
New York, New York, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
...and 7 more locations
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).
Time frame: During course 1 of therapy
Adverse events as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time frame: Weekly during course 1, assessed up to 35 days
Pharmacokinetics of sunitinib malate using liquid spectrometry/mass spectroscopy methods
Time frame: At baseline and days 1, 7, 14, 21, and 28 of course 1
Tolerability and pharmacokinetic profile of capsule contents sprinkled over applesauce or yogurt
Time frame: At baseline and days 1, 7, 14, 21, and 28 of course 1
Correlative studies
The laboratory, radiology, and pathology correlative studies are largely expected to be exploratory. Mean and median values will be reported at each time point for circulating endothelial cells, monocyte count, plasma angiogenic markers, and DCE-MRI vascular permeability. Depending on the distribution of data, either the paired t-test or Wilcoxon signed rank test will be used to evaluate for statistically significant changes in these markers from pre-treatment to post-treatment.
Time frame: Days 1 and 28 of course 1
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