Ignite Creation Date:
2025-12-25 @ 12:09 AM
Ignite Modification Date:
2025-12-30 @ 9:11 PM
Study NCT ID:
NCT00107458
Status:
COMPLETED
Last Update Posted:
2014-08-07
First Post:
2005-04-05
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Valproic Acid in Treating Young Patients With Recurrent or Refractory Solid Tumors or CNS Tumors
Sponsor:
Children's Oncology Group
Organization:
Study Overview
Official Title:
A Phase I Study of Valproic Acid in Children With Recurrent/Progressive Solid Tumors Including CNS Tumors
Status:
COMPLETED
Status Verified Date:
2014-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: