Finding studies
Finding studies
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Lead
National Institutes of Health Clinical Center (CC)
With
OBJECTIVES: Primary * Determine the dose of talabostat, when used in combination with either temozolomide or carboplatin, at which maximum plasma dipeptidyl peptidase IV enzyme inhibition is achieved (in the absence of talabostat-related dose-limiting toxicity) in pediatric patients with refractory or relapsed solid tumors, including brain tumors. * Determine the maximum tolerated dose of talabostat, when used in combination with temozolomide or carboplatin in pediatric patients, if dose-limiting toxicity attributed to talabostat is observed. * Define the toxicity profile of talabostat when used in combination with temozolomide or carboplatin. * Describe the pharmacokinetic profile of talabostat in pediatric patients. Secondary * Study levels, at baseline and after drug administration, of serum cytokines (interleukin \[IL\]-2, IL-6, IL-10, filgrastim \[G-CSF\], tumor necrosis factor-α, IL-1β, IL-8, IP10, and thrombospondin) that may be important in the immune-mediated antitumor effect of talabostat. * Evaluate the antitumor effect of talabostat in combination with temozolomide or carboplatin on pediatric solid tumors by direct assessment of tumor response. * Study the effect of talabostat on neutrophil function. * Evaluate the expression of fibroblast activation protein (FAP) in pediatric tumors using immunohistochemistry to detect FAP in paraffin-embedded tissue sections from existing tumor specimens, when available. OUTLINE: This is a dose-escalation study of talabostat. Patients are stratified according to tumor histology and prior therapy. Based on stratification, patients receive either oral temozolomide on days 1-5 or carboplatin IV over 30 minutes on days 1-2. Patients also receive oral talabostat on days 7-20. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. (Closed to accrual as of 5/25/2009) Cohorts of 2-6 patients receive escalating doses of talabostat until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 or \< 4 of 12 patients experience dose-limiting toxicity during the first course of therapy. PROJECTED ACCRUAL: A total of 26 patients will be accrued for this study.
Age
2–18
Sex
ALL
Healthy volunteers
Not accepted
