Talabostat Combined With Temozolomide or Carboplatin in Treating Young Patients With Relapsed or Refractory Brain Tumors or Other Solid Tumors
Condition: Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Kidney Cancer; Liver Cancer; Neuroblastoma; Ovarian Cancer; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific
MeSH terms: Neoplasms; Sarcoma; Brain Neoplasms; Liver Neoplasms; Neuroblastoma; Neoplasms, Germ Cell and Embryonal; Nervous System Neoplasms; Central Nervous System Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): carboplatin; talabostat mesylate; temozolomide; pharmacological study
Intervention type(s): Drug; Drug; Drug; Other
Intervention MeSH terms: Carboplatin; Temozolomide
Primary purpose: Treatment
Keywords: unspecified childhood solid tumor, protocol specific; recurrent childhood rhabdomyosarcoma; recurrent childhood soft tissue sarcoma; recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor; recurrent osteosarcoma; recurrent neuroblastoma; recurrent Wilms tumor and other childhood kidney tumors; recurrent childhood malignant germ cell tumor; recurrent childhood liver cancer; recurrent childhood brain stem glioma; recurrent childhood cerebellar astrocytoma; recurrent childhood cerebral astrocytoma; recurrent childhood ependymoma; recurrent childhood medulloblastoma; recurrent childhood supratentorial primitive neuroectodermal tumor; childhood atypical teratoid/rhabdoid tumor; childhood low-grade cerebral astrocytoma; childhood high-grade cerebral astrocytoma; childhood choroid plexus tumor; childhood craniopharyngioma; childhood infratentorial ependymoma; childhood supratentorial ependymoma; childhood oligodendroglioma; recurrent childhood visual pathway and hypothalamic glioma; recurrent childhood brain tumor; childhood central nervous system germ cell tumor; childhood grade I meningioma; childhood grade II meningioma; childhood grade III meningioma; childhood malignant ovarian germ cell tumor; childhood malignant testicular germ cell tumor; childhood teratoma