A Phase I Study of Valproic Acid in Children With Recurrent/Progressive Solid Tumors Including CNS Tumors
- 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.
- 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
- 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.
Primary Purpose: Treatment
Jack M. Su, MD
Texas Children's Cancer Center
United States: Federal Government
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Mayo Clinic Cancer Center||Rochester, Minnesota 55905|
|Children's Hospital of Orange County||Orange, California 92668|
|Children's National Medical Center||Washington, District of Columbia 20010-2970|
|Children's Hospital and Regional Medical Center - Seattle||Seattle, Washington 98105|
|Children's Memorial Hospital - Chicago||Chicago, Illinois 60614|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute||Boston, Massachusetts 02115|
|SUNY Upstate Medical University Hospital||Syracuse, New York 13210|
|Cincinnati Children's Hospital Medical Center||Cincinnati, Ohio 45229-3039|
|Baylor University Medical Center - Houston||Houston, Texas 77030-2399|
|Indiana University Melvin and Bren Simon Cancer Center||Indianapolis, Indiana 46202-5289|
|Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center||New York, New York 10032|
|Oregon Health & Science University Cancer Institute||Portland, Oregon 97239-3098|
|Stanford Comprehensive Cancer Center - Stanford||Stanford, California 94305|
|University of Minnesota Children's Hospital - Fairview||Minneapolis, Minnesota 55455|