Tetra-O-Methyl Nordihydroguaiaretic Acid in Treating Patients With Recurrent High-Grade Glioma - Full Text View

Sponsored by:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00404248

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 I Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
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:

MedlinePlus related topics: Cancer

Drug Information available for: Masoprocol Tetramethoxynordihydroguaiaretic acid

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

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 ]

Estimated Enrollment:	50
Study Start Date:	January 2007
Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Detailed Description:

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

National Cancer Institute (NCI)

Investigators

Study Chair:

Stuart A. Grossman, MD

Sidney Kimmel Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	New Approaches to Brain Tumor Therapy ( Stuart A. Grossman )
Study ID Numbers:	CDR0000515952, NABTT-0503
Study First Received:	November 27, 2006
Last Updated:	June 23, 2009
ClinicalTrials.gov Identifier:	NCT00404248 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
adult giant cell glioblastoma

recurrent adult brain tumor
adult glioblastoma
adult gliosarcoma

Study placed in the following topic categories:

Anti-Inflammatory Agents
Glioblastoma
Antioxidants
Astrocytoma
Cyclooxygenase Inhibitors
Central Nervous System Neoplasms
Recurrence
Lipoxygenase Inhibitors
Brain Neoplasms
Nordihydroguaiaretic Acid

Analgesics, Non-Narcotic
Anti-Inflammatory Agents, Non-Steroidal
Oligodendroglioma
Peripheral Nervous System Agents
Analgesics
Glioma
Antirheumatic Agents
Gliosarcoma
Nervous System Neoplasms

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Cyclooxygenase Inhibitors
Nervous System Diseases
Physiological Effects of Drugs
Enzyme Inhibitors
Central Nervous System Neoplasms
Protective Agents
Lipoxygenase Inhibitors
Pharmacologic Actions
Nordihydroguaiaretic Acid

Neoplasms
Neoplasms by Site
Sensory System Agents
Analgesics, Non-Narcotic
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Peripheral Nervous System Agents
Analgesics
Antirheumatic Agents
Central Nervous System Agents
Nervous System Neoplasms

ClinicalTrials.gov processed this record on September 03, 2009