Tetra-O-Methyl Nordihydroguaiaretic Acid in Treating Patients With Recurrent High-Grade Glioma
This study has been completed.
Sponsor:
Sidney Kimmel Comprehensive Cancer Center
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00404248
First received: November 27, 2006
Last updated: May 1, 2012
Last verified: May 2012
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Brain and Central Nervous System Tumors |
Drug: terameprocol Other: pharmacological study |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| 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 |
Resource links provided by NLM:
Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:
Primary Outcome Measures:
- Maximum tolerated dose (Phase I) [ Designated as safety issue: Yes ]
- Response rate (Phase II) [ Designated as safety issue: No ]
Secondary Outcome Measures:
- 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 ]
| Enrollment: | 35 |
| Study Start Date: | January 2007 |
| Study Completion Date: | February 2012 |
| Primary Completion Date: | June 2009 (Final data collection date for primary outcome measure) |
OBJECTIVES:
Primary
- 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)
Secondary
- 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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed malignant glioma, including any of the following subtypes:
- Anaplastic astrocytoma
- Anaplastic oligodendroglioma
- Glioblastoma multiforme
Progressive or recurrent disease after radiation therapy with or without chemotherapy
- Patients with a previous low-grade glioma that has progressed to biopsy-confirmed high-grade glioma after radiation therapy with or without chemotherapy are eligible
- Contrast-enhancing measurable disease by MRI or CT scan
PATIENT CHARACTERISTICS:
- Karnofsky performance status 60-100%
- Absolute neutrophil count ≥ 1,500/mm³
- Hemoglobin ≥ 9 g/dL
- Platelet count ≥ 100,000/mm³
- Creatinine ≤ 1.5 mg/dL
- Bilirubin ≤ 1.5 mg/dL
- Transaminases ≤ 4 times upper limit of normal
- PT/PTT/INR normal
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception during and for 2 months after completion of study treatment
- Mini Mental State Exam score ≥ 15
- No serious concurrent infection or medical illness that would impair the ability to safely receive study treatment
- No other prior or concurrent malignancy within the past 5 years except for curatively treated carcinoma in situ or basal cell carcinoma of the skin
- No known sensitivity to any of the study medication components (i.e., polyethylene glycol [PEG 300] and 2-hydroxypropyl β-cyclodextrin)
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered from prior therapy
- At least 3 months since prior radiation therapy
- At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)
- At least 2 weeks since prior Federal Drug Administration (FDA)-approved noncytotoxic therapy (e.g., celecoxib or thalidomide)
- At least 3 weeks since prior investigational noncytotoxic agents
At least 10 days since prior anticonvulsant drugs that induce hepatic metabolic enzymes, including any of the following:
- Phenytoin
- Carbamazepine
- Phenobarbital
- Primidone
- Oxcarbazepine
- Ethosuximide
No other concurrent therapy for this tumor, including systemic chemotherapy or radiation therapy
- Concurrent steroids allowed
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00404248
Locations
| 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 | |
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
| Study Chair: | Stuart A. Grossman, MD | Sidney Kimmel Comprehensive Cancer Center |
More Information
Additional Information:
Publications:
| Responsible Party: | Sidney Kimmel Comprehensive Cancer Center |
| ClinicalTrials.gov Identifier: | NCT00404248 History of Changes |
| Other Study ID Numbers: | NABTT-0503 CDR0000515952, U01CA062475, NABTT-0503 |
| Study First Received: | November 27, 2006 |
| Last Updated: | May 1, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
|
adult anaplastic astrocytoma adult anaplastic oligodendroglioma adult giant cell glioblastoma |
recurrent adult brain tumor adult glioblastoma adult gliosarcoma |
Additional relevant MeSH terms:
|
Nervous System Neoplasms Central Nervous System Neoplasms Neoplasms by Site Neoplasms Nervous System Diseases Nordihydroguaiaretic Acid Lipoxygenase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antioxidants Protective Agents |
Physiological Effects of Drugs Cyclooxygenase Inhibitors Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Anti-Inflammatory Agents Therapeutic Uses Central Nervous System Agents Antirheumatic Agents |
ClinicalTrials.gov processed this record on May 19, 2013