Clinical Trial: Sunitinib in Treating Young Patients With Refractory Solid Tumors

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I Study of Sunitinib (SU11248), an Oral Multi-Targeted Tyrosine Kinase Inhibitor, in Children With Refractory Solid Tumors

Brief Summary: 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.

Detailed Summary:

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 rec
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • MTD and recommended phase II dose [ Time Frame: During course 1 of therapy ]
    MTD will be the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT).
  • 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 ]


Original Primary Outcome:

Current Secondary Outcome: Correlative studies [ Time Frame: Days 1 and 28 of course 1 ]

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.


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: October 12, 2006
Date Started: October 2006
Date Completion:
Last Updated: January 27, 2014
Last Verified: January 2014