Valproic Acid in Treating Young Patients With Recurrent or Refractory Solid Tumors or CNS Tumors
Condition: Brain and Central Nervous System Tumors; Unspecified Childhood Solid Tumor, Protocol Specific
MeSH terms: Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as valproic acid, work in different ways to stop
      the growth of tumor cells, either by killing the cells or by stopping them from dividing.
      Valproic acid may also stop the growth of solid tumors or CNS tumors by blocking blood flow
      to the tumor.

      PURPOSE: This phase I trial is studying the side effects and best dose of valproic acid in
      treating patients with recurrent or refractory solid tumors or CNS tumors.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine the toxic effects of valproic acid (VPA) administered at doses required to
           maintain serum trough VPA concentrations of 100-150 mcg/mL or 150-200 mcg/mL in young
           patients with recurrent or refractory solid tumors or CNS tumors.

      Secondary

        -  Determine the steady-state serum trough concentration of free and total VPA at the
           targeted total trough VPA concentration in these patients.

        -  Determine the steady state histone acetylation status of peripheral blood monocytes at
           the targeted trough VPA concentration in these patients.

        -  Determine the pharmacokinetic profile of this drug in these patients.

        -  Correlate histone acetylation with free or total trough VPA concentration in these
           patients.

        -  Determine, preliminarily, the antitumor activity of this drug in these patients.

      OUTLINE: This is a dose-escalation, multicenter study.

      For course 1, patients receive escalating doses of oral valproic acid (VPA) twice daily until
      a target serum trough VPA concentration range is maintained for 28 days. Patients who achieve
      the target serum trough VPA concentration range receive subsequent courses of oral VPA twice
      daily (at the dose found to maintain the target serum trough VPA concentration range) on days
      1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease
      progression or unacceptable toxicity.

      The first cohort of 6 patients receives VPA to achieve an initial target trough serum VPA
      concentration. If fewer than 2 of 6 patients in the first cohort experience dose-limiting
      toxicity (DLT), then a second cohort of 6 patients receives VPA to achieve the next higher
      target trough serum VPA concentration. If fewer than 2 patients from the second cohort
      experience DTL, then 6 additional patients are enrolled in this cohort to better define
      pharmacokinetics and DLT at this VPA concentration range.

      After completion of study treatment, patients are followed annually.

      PROJECTED ACCRUAL: A total of 12-18 patients will be accrued for this study.
    

Intervention name(s): valproic acid
Intervention type(s): Drug
Intervention MeSH terms: Valproic Acid
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: recurrent childhood brain stem glioma; recurrent childhood brain tumor; recurrent childhood cerebellar astrocytoma; recurrent childhood cerebral astrocytoma; recurrent childhood ependymoma; recurrent childhood medulloblastoma; recurrent childhood supratentorial primitive neuroectodermal tumor; unspecified childhood solid tumor, protocol specific; recurrent childhood visual pathway and hypothalamic glioma; childhood high-grade cerebral astrocytoma; childhood low-grade cerebral astrocytoma; childhood infratentorial ependymoma; childhood supratentorial ependymoma; childhood spinal cord neoplasm; childhood grade I meningioma; childhood grade II meningioma; childhood grade III meningioma; childhood craniopharyngioma; childhood central nervous system germ cell tumor