A Phase I Trial and Pharmacokinetic Study of Talabostat (PT-100, Val-Boro-Pro) in Combination With Temozolomide or Carboplatin in Pediatric Patients With Relapsed or Refractory Solid Tumors Including Brain Tumors
- 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
- Describe the pharmacokinetic profile of talabostat in pediatric patients.
- 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.
Primary Purpose: Treatment
Holly Meany, MD
National Cancer Institute (NCI)
United States: Food and Drug Administration
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office||Bethesda, Maryland 20892-1182|