This phase I trial studies the side effects and best dose of terameprocol in treating patients with high-grade glioma that has come back. Drugs used in chemotherapy, such as terameprocol, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) of terameprocol given orally on days 1-5 every 28 days in patients with high grade glioma. (Part 1) II. To evaluate terameprocol tumor to plasma ratios in resected high grade gliomas following 5 days of oral terameprocol administration. (Part 2) III. To assess the maximum duration of terameprocol that can be safely administered on a continuous basis. (Part 3) SECONDARY OBJECTIVES: I. Characterize the plasma pharmacokinetic (PK) of oral terameprocol. II. Evaluate the toxicities of oral terameprocol. III. Assess progression-free survival. IV. Estimate overall survival. V. Assess tumor response. TERTIARY OBJECTIVES: I. Assess the contribution of cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) genotypes on the variability of oral terameprocol pharmacokinetics. OUTLINE: This is a dose-escalation study. Patients receive terameprocol orally (PO) once daily (QD) on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days, every 2 months for 2 years, and then every 6 months thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Given PO
Correlative studies
UAB Comprehensive Cancer Center
Birmingham, Alabama, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Maximum tolerated dose of terameprocol (Part 1)
To estimate the MTDs in terms of clinical toxicities, a modified continual reassessment method, based on that described by Piantadosi et al. will be employed. Dose escalation will be guided by observed clinical toxicity in 3 patients per dose cohort after the initial dose.
Time frame: Day 1 - Day28 (First Cycle)
Change in terameprocol tumor to plasma concentration ratio (Part 2)
The tumor/plasma concentration ratio will be estimated.
Time frame: Baseline, Pre-surgery (shortly before start of surgery - within 1hr) and post surgery (as soon as practical afer completion of surgery - approx 4 hrs)
Maximum tolerated days of terameprocol dosing that can safely be administered on a continuous basis (Part 3)
This is a escalation study. The escalation is the number of continuous days that terameprocol can be given. Terameprocol dose will remain constant at a fix dose everyday.
Time frame: Up to 28 days
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Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States
Abrams Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States