This phase I/II trial is studying the side effects and best dose of imatinib mesylate and to see how well it works in treating patients with a recurrent brain tumor that has not responded to previous surgery and radiation therapy. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.
PRIMARY OBJECTIVES: I. To identify the maximum tolerated dose of imatinib (imatinib mesylate) in patients with recurrent oligodendroglioma and mixed oligoastrocytoma that are currently on enzyme inducing anticonvulsant therapy. (Study 1) II. To assess the efficacy of imatinib in patients with recurrent oligodendrogliomas and mixed oligoastrocytomas (with pathologic evidence of oligodendrogliomatous component) as measured by progression-free survival, response, and overall survival. (Study 2) III. To acquire pilot data on a patient group not traditionally eligible for recurrent oligodendroglioma and mixed oligoastrocytoma clinical trials (those having \> 2 prior chemotherapy regimens or 2 prior chemotherapy regimens for recurrent/progressive disease). (Study 3) IV. To examine the toxicity and safety of imatinib in patients with recurrent oligodendrogliomas and mixed oligoastrocytomas (with pathologic evidence of oligodendrogliomatous component). (Studies 1, 2, and 3) V. To perform a preliminary correlative study of 1p/19q alterations, alpha platelet-derived growth factor receptor (PDFGR) gene amplification and levels of related downstream signaling elements in tumor tissue, with clinical study endpoints. (Studies 1, 2, and 3) VI. To perform a descriptive correlative analysis of steady state pharmacokinetic data regarding imatinib and active metabolites with the study endpoints. (Studies 1, 2, and 3) OUTLINE: This is a phase I, dose-escalation study followed by a phase II and a pilot study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
Given PO
Optional correlative studies
Optional correlative studies
6-month Progression-free Survival (PFS), Defined as a Patient Being Alive and Progression-free 183 Days After the Date of Registration.
The proportion of successes will be estimated using the Binomial point estimator (number of successes divided by the total number of evaluable patients) and the Binomial 90% confidence interval estimated using the Duffy-Santer algorithm. Progression is defined using response criteria (the neurologic examination and the MRI and/or CT), \>25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions.
Time frame: 6 months
Confirmed Response (i.e., an Objective Status of Complete Response (CR), Partial Response (PR), or Regression (REGR) on 2 Successive Evaluations at Least 4 Weeks Apart After the Start of Study Treatment).
Complete Response (CR) is defined using response criteria (the neurologic examination and the Magnetic resonance imaging (MRI) and/or Computerized Tomography (CT)), total disappearance of all tumor with patient off corticosteroids or only on adrenal replacement maintenance. Partial Response (PR) is defined using response criteria (the neurologic examination and the MRI and/or CT), \>=50% reduction in product of perpendicular diameters of contrast enhancement or mass with no new lesions with the patient being on stable or decreased steroid dose. Regression (REGR) is defined using response criteria (the neurologic examination and the MRI and/or CT), unequivocal reduction in size of contrast-enhancement or decrease in mass effect as agreed upon independently by primary physician and quality control physicians; no new lesions. Patient should be on stable or decreased steroid dose.
Time frame: Up to 5 years
Percentage of Patients Progression-free
The percentage of patient progression-free at 12 months, 18 months, and PFS will be estimated. Kaplan-Meier survival curves and logrank tests will be used to estimate progression-time distributions. Progression is defined using response criteria (the neurologic examination and the MRI and/or CT), \>25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions.
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Mayo Clinic in Arizona
Scottsdale, Arizona, United States
Saint Francis Hospital and Medical Center
Hartford, Connecticut, United States
Mayo Clinic in Florida
Jacksonville, Florida, United States
Rush - Copley Medical Center
Aurora, Illinois, United States
Bromenn Lifecare Center
Bloomington, Illinois, United States
Saint Joseph Medical Center
Bloomington, Illinois, United States
Graham Hospital Association
Canton, Illinois, United States
Memorial Hospital
Carthage, Illinois, United States
Eureka Hospital
Eureka, Illinois, United States
Galesburg Cottage Hospital
Galesburg, Illinois, United States
...and 219 more locations
Time frame: Time from study registration to date of disease progression or last follow-up, assessed up to 5 years
Overall Time to Death
Kaplan-Meier survival curves and logrank tests will be used to estimate survival distributions.
Time frame: Time from date of registration to date of death due to any cause or last follow-up, assessed up to 5 years