Valproic Acid in Treating Young Patients With Recurrent or Refractory Solid Tumors or CNS Tumors
|ClinicalTrials.gov Identifier: NCT00107458|
Recruitment Status : Completed
First Posted : April 6, 2005
Last Update Posted : August 7, 2014
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.
|Condition or disease||Intervention/treatment||Phase|
|Brain and Central Nervous System Tumors Unspecified Childhood Solid Tumor, Protocol Specific||Drug: valproic acid||Phase 1|
- 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 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Official Title:||A Phase I Study of Valproic Acid in Children With Recurrent/Progressive Solid Tumors Including CNS Tumors|
|Study Start Date :||May 2005|
|Actual Primary Completion Date :||October 2007|
|Actual Study Completion Date :||March 2012|
Experimental: Treatment 1
VPA Target Trough Concentration 75-100 mcg/mL, week 1 VPA dose: 15 mg/kg/day, divided tid
|Drug: valproic acid|
Experimental: Treatment 10
VPA Target Trough Concentration 100-150 mcg/mL, week 1 VPA dose: 15 mg/kg/day, divided tid
|Drug: valproic acid|
Experimental: Treatment 20
VPA Target Trough Concentration 150-200 mcg/mL
|Drug: valproic acid|
- Efficacy of oral etoposide at 50 mg/m2/day given concurrently with radiotherapy
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00107458
|United States, California|
|Children's Hospital of Orange County|
|Orange, California, United States, 92868|
|Stanford Comprehensive Cancer Center - Stanford|
|Stanford, California, United States, 94305|
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010-2970|
|United States, Illinois|
|Children's Memorial Hospital - Chicago|
|Chicago, Illinois, United States, 60614|
|United States, Indiana|
|Indiana University Melvin and Bren Simon Cancer Center|
|Indianapolis, Indiana, United States, 46202-5289|
|United States, Massachusetts|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, Minnesota|
|University of Minnesota Children's Hospital - Fairview|
|Minneapolis, Minnesota, United States, 55455|
|Mayo Clinic Cancer Center|
|Rochester, Minnesota, United States, 55905|
|United States, New York|
|Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center|
|New York, New York, United States, 10032|
|SUNY Upstate Medical University Hospital|
|Syracuse, New York, United States, 13210|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229-3039|
|United States, Oregon|
|Oregon Health & Science University Cancer Institute|
|Portland, Oregon, United States, 97239-3098|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104-9786|
|United States, Texas|
|Baylor University Medical Center - Houston|
|Houston, Texas, United States, 77030-2399|
|United States, Washington|
|Children's Hospital and Regional Medical Center - Seattle|
|Seattle, Washington, United States, 98105|
|Hospital for Sick Children|
|Toronto, Ontario, Canada, M5G 1X8|
|Hopital Sainte Justine|
|Montreal, Quebec, Canada, H3T 1C5|
|Study Chair:||Jack M. Su, MD||Texas Children's Cancer Center|
|Study Chair:||Heidi V. Russell, MD||Texas Children's Cancer Center|