Valproic Acid in Treating Young Patients With Recurrent or Refractory Solid Tumors or CNS Tumors
- Conditions
- Unspecified Childhood Solid Tumor, Protocol SpecificBrain and Central Nervous System Tumors
- Interventions
- Registration Number
- NCT00107458
- Lead Sponsor
- Children's Oncology Group
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 26
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment 20 valproic acid VPA Target Trough Concentration 150-200 mcg/mL Treatment 1 valproic acid VPA Target Trough Concentration 75-100 mcg/mL, week 1 VPA dose: 15 mg/kg/day, divided tid Treatment 10 valproic acid VPA Target Trough Concentration 100-150 mcg/mL, week 1 VPA dose: 15 mg/kg/day, divided tid
- Primary Outcome Measures
Name Time Method Efficacy of oral etoposide at 50 mg/m2/day given concurrently with radiotherapy
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (17)
Hopital Sainte Justine
🇨🇦Montreal, Quebec, Canada
Children's Memorial Hospital - Chicago
🇺🇸Chicago, Illinois, United States
Indiana University Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
SUNY Upstate Medical University Hospital
🇺🇸Syracuse, New York, United States
Oregon Health & Science University Cancer Institute
🇺🇸Portland, Oregon, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Minnesota Children's Hospital - Fairview
🇺🇸Minneapolis, Minnesota, United States
Stanford Comprehensive Cancer Center - Stanford
🇺🇸Stanford, California, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Baylor University Medical Center - Houston
🇺🇸Houston, Texas, United States
Children's Hospital and Regional Medical Center - Seattle
🇺🇸Seattle, Washington, United States
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
🇺🇸New York, New York, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States