Phase I/II Study of Intravenous Infusion of Tetra-o-Methyl Nordihydroguaiaretic Acid (EM-1421) in Subjects With Recurrent High Grade Glioma
- 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.
- 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.
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
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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (Phase I)
Stuart A. Grossman, MD
Sidney Kimmel Comprehensive Cancer Center
United States: Food and Drug Administration
|Abramson Cancer Center of the University of Pennsylvania||Philadelphia, Pennsylvania 19104-4283|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|
|Cleveland Clinic Taussig Cancer Center||Cleveland, Ohio 44195|
|Josephine Ford Cancer Center at Henry Ford Hospital||Detroit, Michigan 48202|
|Winship Cancer Institute of Emory University||Atlanta, Georgia 30322|
|Wake Forest University Comprehensive Cancer Center||Winston-Salem, North Carolina 27157-1096|
|Massachusetts General Hospital||Boston, Massachusetts 02114-2617|
|H. Lee Moffitt Cancer Center and Research Institute at University of South Florida||Tampa, Florida 33612|
|UAB Comprehensive Cancer Center||Birmingham, Alabama 35294|