Imatinib Mesylate in Treating Patients With Recurrent Brain Tumor
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
Adult Anaplastic Oligodendroglioma
Adult Mixed Glioma
Recurrent Adult Brain Tumor
Drug: imatinib mesylate
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Trial Of Imatinib Mesylate; (Gleevec; STI571) In Treatment Of Recurrent Oligodendroglioma And Mixed Oligoastrocytoma|
- MTD of imatinib mesylate when given to patients who are receiving EIACs, defined as the highest safely tolerated dose level where, at most, 1 of 6 patients experiences DLT, graded according to CTCAE v4.0 (Phase I) [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: Yes ]
- 6-month progression-free survival (PFS), defined as a patient being alive and progression-free 183 days after the date of registration (Phase II and Pilot) [ Time Frame: 6 months ] [ Designated as safety issue: No ]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-Santner algorithm.
- Confirmed response (i.e., an objective status of CR, PR, or REGR on 2 successive evaluations at least 4 weeks apart after the start of study treatment) (Phase II and Pilot) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- Percentage of patients progression-free (Phase II and Pilot) [ Time Frame: Time from study registration to date of disease progression or last follow-up, assessed up to 5 years ] [ Designated as safety issue: No ]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.
- Overall time to death (Phase II and Pilot) [ Time Frame: Time from date of registration to date of death due to any cause or last follow-up, assessed up to 5 years ] [ Designated as safety issue: No ]Kaplan-Meier survival curves and logrank tests will be used to estimate survival distributions.
- Quality of life as assessed by five Linear Analogue Self Assessment (LASA) items (Phase II and Pilot) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
|Study Start Date:||June 2003|
|Primary Completion Date:||August 2011 (Final data collection date for primary outcome measure)|
Experimental: Phase II group 1
Patients receive oral imatinib mesylate, at the MTD determined in phase I, twice daily for 4 weeks.
Drug: imatinib mesylate
Experimental: Phase II group 2
Patients receive oral standard-dose imatinib mesylate twice daily for 4 weeks.
Drug: imatinib mesylate
I. Determine the maximum tolerated dose of imatinib mesylate in patients with recurrent oligodendroglioma or mixed oligoastrocytoma who are currently on enzyme-inducing anticonvulsant therapy.
II. Determine the efficacy of imatinib mesylate, as measured by response, survival, and progression-free survival, in patients with recurrent oligodendroglioma or mixed oligoastrocytoma.
III. Compare pilot data of patients who have undergone > 2 prior chemotherapy regimens for recurrent, progressive, or mixed oligodendroglioma with traditional patients with recurrent or mixed oligodendroglioma.
IV. Determine the toxicity and safety of this drug in these patients. V. Correlate, preliminarily, 1p/19q alterations, alpha-PDFGR gene amplification, and levels of related downstream signaling elements in tumor tissue with clinical response in patients treated with this drug.
OUTLINE: This is a multicenter, phase I, dose-escalation study followed by a phase II and a pilot study.
PHASE I: Patients receive oral imatinib mesylate twice daily for 4 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of imatinib mesylate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
GROUP 1 (CONCURRENT ENZYME-INDUCING ANTICONVULSANTS [EIACs]): Patients receive oral imatinib mesylate, at the MTD determined in phase I, twice daily for 4 weeks.
GROUP 2 (NON-EIACs): Patients receive oral standard-dose imatinib mesylate twice daily for 4 weeks.
In both groups, treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
PILOT STUDY: Patients are stratified and assigned to treatment groups as in phase II. Patients receive oral imatinib as in phase II.
Patients are followed every 2 months.