This phase I trial is studying the side effects and best dose of pazopanib hydrochloride in treating young patients with solid tumors that have relapsed or not responded to treatment. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
PRIMARY OBJECTIVES: I. Estimate the maximum-tolerated dose and/or recommended phase II dose of pazopanib hydrochloride in pediatric patients with relapsed or refractory solid tumors. II. Define and describe the toxicities of this regimen in these patients. III. Characterize the pharmacokinetics of pazopanib hydrochloride in these patients. SECONDARY OBJECTIVES: I. Preliminarily define the antitumor activity of pazopanib hydrochloride within the confines of a phase I study. II. Evaluate changes in tumor vascular permeability following initiation of pazopanib hydrochloride and correlate these changes with clinical outcome by dynamic contrast-enhanced MRI. OUTLINE: This is a multicenter study dose-escalation study. Patients receive oral pazopanib hydrochloride once daily on days 1-28. Courses repeat every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. Patients accrued after the maximum-tolerated dose (MTD) of pazopanib hydrochloride has been determined receive pazopanib hydrochloride as an oral suspension. Some patients undergo dynamic contrast-enhanced MRI at baseline and periodically during study. Blood samples are collected at baseline and periodically during study for pharmacokinetic studies.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
55
Given orally
Correlative studies
University of Alabama at Birmingham
Birmingham, Alabama, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
Indiana University Medical Center
Indianapolis, Indiana, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, United States
Columbia University Medical Center
New York, New York, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Oregon Health and Science University
Portland, Oregon, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
...and 4 more locations
Maximum-tolerated dose of pazopanib hydrochloride defined as the maximum dose at which fewer that one-third of patients experience DLT
Graded using the NCI CTCAE version 4.0.
Time frame: 28 days
Adverse events according to NCI CTCAE version 4.0
Time frame: Up to 30 days after completion of study treatment
Pharmacokinetics of pazopanib hydrochloride
Summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
Time frame: Baseline, days 15, 22, and 27 of course 1 and day 1 of odd courses
Overall response to pazopanib hydrochloride according to RECIST criteria
The overall response assessment takes into account response in both target and non-target lesions, the appearance of new lesions and normalization of markers.
Time frame: Up to 30 days after completion of study treatment
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