Talabostat Combined With Temozolomide or Carboplatin in Treating Young Patients With Relapsed or Refractory Brain Tumors or Other Solid Tumors
RATIONALE: Talabostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving talabostat together with temozolomide or carboplatin may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of talabostat when given together with temozolomide or carboplatin in treating young patients with relapsed or refractory brain tumors or other solid tumors.
|Brain and Central Nervous System Tumors Childhood Germ Cell Tumor Kidney Cancer Liver Cancer Neuroblastoma Ovarian Cancer Sarcoma Unspecified Childhood Solid Tumor, Protocol Specific||Drug: carboplatin Drug: talabostat mesylate Drug: temozolomide Other: pharmacological study||Phase 1|
|Study Design:||Primary Purpose: Treatment|
|Official Title:||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|
|Study Start Date:||December 2005|
|Study Completion Date:||February 2010|
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00303940
|United States, Maryland|
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office|
|Bethesda, Maryland, United States, 20892-1182|
|Study Chair:||Holly Meany, MD||National Cancer Institute (NCI)|
|Principal Investigator:||Elizabeth Fox, MD||National Cancer Institute (NCI)|