Tetra-O-Methyl Nordihydroguaiaretic Acid in Treating Patients With Recurrent High-Grade Glioma
RATIONALE: Drugs used in chemotherapy, such as tetra-O-methyl nordihydroguaiaretic acid (EM-1421), work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This phase I/II trial is studying the side effects and best dose of EM-1421 and to see how well it works in treating patients with recurrent high-grade glioma.
Brain and Central Nervous System Tumors
Other: pharmacological study
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Intravenous Infusion of Tetra-o-Methyl Nordihydroguaiaretic Acid (EM-1421) in Subjects With Recurrent High Grade Glioma|
- Maximum tolerated dose (Phase I) [ Designated as safety issue: Yes ]
- Response rate (Phase II) [ Designated as safety issue: No ]
- Pharmacokinetics (Phase I) [ Designated as safety issue: No ]
- Toxicity (Phase I) [ Designated as safety issue: Yes ]
- Effects of hepatic enzyme-inducing anticonvulsants on the pharmacokinetic profile (Phase I) [ Designated as safety issue: No ]
- Safety (Phase II) [ Designated as safety issue: Yes ]
- Tolerability (Phase I and II) [ Designated as safety issue: Yes ]
- Overall survival (Phase I and II) [ Designated as safety issue: No ]
- Treatment response (complete and partial remission and stable disease) (Phase II) [ Designated as safety issue: No ]
|Study Start Date:||January 2007|
|Study Completion Date:||February 2012|
|Primary Completion Date:||June 2009 (Final data collection date for primary outcome measure)|
- Determine the maximum tolerated dose (MTD) of tetra-O-methyl nordihydroguaiaretic acid (EM-1421) in patients with recurrent high-grade glioma. (Phase I)
- Determine the response rate in patients treated with EM-1421 administered at the MTD. (Phase II)
- Describe the pharmacokinetics of EM-1421 in these patients. (Phase I)
- Determine the effects of hepatic enzyme-inducing anticonvulsants on the pharmacokinetic profile of EM-1421 in these patients. (Phase I)
- Determine the toxicity of this drug in these patients. (Phase I)
- Assess the tolerability of this drug in these patients. (Phase I)
- Assess the antitumor activity of this drug, in terms of overall survival. (Phase I)
- Assess the overall survival of these patients. (Phase II)
- Assess the safety and tolerability of EM-1421 given at the MTD in these patients. (Phase II)
OUTLINE: This is a multicenter, phase I, dose-escalation study followed by a phase II, open-label study. Patients are stratified according to the use of cytochrome P450-inducing anticonvulsants (use of anticonvulsant drugs that induce hepatic metabolic enzymes vs use of anticonvulsant drugs that cause modest or no induction of hepatic metabolic enzymes or no use of anticonvulsant drugs).
- Phase I: Patients receive tetra-O-methyl nordihydroguaiaretic acid (EM-1421) IV on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of EM-1421 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients receive EM-1421 as in phase I at the MTD. Blood is collected on days 1 and 5 of courses 1 and 2 of treatment for pharmacokinetic studies.
After completion of study therapy, patients are followed every 2 months.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
|United States, Alabama|
|UAB Comprehensive Cancer Center|
|Birmingham, Alabama, United States, 35294-3410|
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute at University of South Florida|
|Tampa, Florida, United States, 33612-9497|
|United States, Georgia|
|Winship Cancer Institute of Emory University|
|Atlanta, Georgia, United States, 30322|
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231|
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|United States, Michigan|
|Josephine Ford Cancer Center at Henry Ford Hospital|
|Detroit, Michigan, United States, 48202|
|United States, North Carolina|
|Wake Forest University Comprehensive Cancer Center|
|Winston-Salem, North Carolina, United States, 27157-1096|
|United States, Ohio|
|Cleveland Clinic Taussig Cancer Center|
|Cleveland, Ohio, United States, 44195|
|United States, Pennsylvania|
|Abramson Cancer Center of the University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104-4283|
|Study Chair:||Stuart A. Grossman, MD||Sidney Kimmel Comprehensive Cancer Center|