Phase 2 N=35 Treatment

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

Brain and Central Nervous System Tumors

Bottom Line

View on ClinicalTrials.gov: NCT00404248 ↗

Enrolled (actual)

Serious AEs

11.4%

Results posted

Aug 2015

Primary outcome: Primary: Maximum Tolerated Dose (Phase I) — 1700; 1700; 1700 mg/day x 5 days

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: terameprocol (Drug); pharmacological study (Other)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Primary completion: Jun 2009

Outcome Measures

Outcome	Result	p-value
PRIMARY Maximum Tolerated Dose (Phase I)	1700; 1700; 1700	—
PRIMARY Maximum Tolerated Dose (Phase I) - Dose Limiting Toxicity (DLT)	0; 0; 0; 0; 0; 0	—
SECONDARY Pharmacokinetics - Total Body Clearance	53.7; 54.4	0.9
SECONDARY Pharmacokinetics - Steady-State Apparent Volume Distribution	706; 612	0.6
SECONDARY Pharmacokinetics - Terminal Phase Half-life	18.2; 17.1	0.8
SECONDARY Efficacy - Best Overall Response	0; 0; 23; 9	—
SECONDARY Survival	5.5	—

Summary

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.

Eligibility 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
Prothrombin Time (PT)/partial thromboplastin time (PTT) /international normalized ratio (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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00404248). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.