Overview

This trial is active, not recruiting.

Conditions adult anaplastic oligodendroglioma, adult mixed glioma, adult oligodendroglioma, recurrent adult brain tumor
Treatment imatinib mesylate
Phase phase 1/phase 2
Sponsor National Cancer Institute (NCI)
Start date June 2003
End date August 2011
Trial size 93 participants
Trial identifier NCT00049127, CDR0000257812, N0272, NCI-2011-01576, U10CA025224

Summary

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients receive oral imatinib mesylate, at the MTD determined in phase I, twice daily for 4 weeks.
imatinib mesylate CGP 57148
Given orally
(Experimental)
Patients receive oral standard-dose imatinib mesylate twice daily for 4 weeks.
imatinib mesylate CGP 57148
Given orally

Primary Outcomes

Measure
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
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

Secondary Outcomes

Measure
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
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
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
Quality of life as assessed by five Linear Analogue Self Assessment (LASA) items (Phase II and Pilot)
time frame: Up to 5 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Histologically confirmed oligodendroglioma or mixed oligoastrocytoma - Grade 2-4 - Recurrent disease - Patients with mixed gliomas must have > 25% oligodendrogliomatous component - Failed prior surgery, radiotherapy, and temozolomide or nitrosourea-based therapy - Progressive disease by MRI or CT scan - Measurable or evaluable disease by MRI or CT scan - More than 2 prior chemotherapy regimens for progressive or recurrent disease (pilot study only) - Currently taking anticonvulsants which can induce cytochrome p450 (e.g., phenytoin, carbamazepine, barbiturates, or primidone (Phase I only) - No prior or concurrent significant intratumoral hemorrhage - Performance status - ECOG 0-2 - Absolute neutrophil count at least 1,500/mm^3 - Platelet count at least 100,000/mm^3 - Hemoglobin at least 9 g/dL - Bilirubin no greater than 1.5 mg/dL - AST no greater than 3 times upper limit of normal - Creatinine no greater than 2.0 mg/dL - No myocardial infarction within the past 6 months - No congestive heart failure requiring maintenance therapy for life-threatening ventricular arrhythmias - No New York Heart Association class III or IV heart disease - No active uncontrolled infection - No other severe concurrent disease that would preclude study or interfere significantly with interpreting potential drug-induced toxic effects - No other active malignancy except nonmelanoma skin cancer - No concurrent serious immunocompromised status unless related to concurrent steroids - HIV-positive patients allowed - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 6 months after study participation - At least 2 weeks since prior biologic noncytotoxic agents (e.g., thalidomide or interferon) - No concurrent biologic therapy or immunotherapy for brain cancer - No concurrent therapeutic warfarin or heparin - Low-dose warfarin and heparin (1 mg daily) allowed - No prior interstitial chemotherapy, including carmustine wafers, unless separate lesion seen on MRI outside of prior treatment field - At least 2 weeks since prior vincristine - At least 4 weeks since other prior chemotherapy (6 weeks for nitrosoureas) - No concurrent chemotherapy for brain cancer - At least 2 weeks since prior tamoxifen - Concurrent corticosteroids allowed if dose stable for at least 1 week prior to study entry - No concurrent hormonal therapy for brain cancer - At least 12 weeks since prior radiotherapy - No prior stereotactic radiosurgery or interstitial brachytherapy unless separate lesion seen on MRI outside of prior treatment field - No concurrent radiotherapy for brain cancer - No other concurrent investigational or noninvestigational therapy for brain cancer - At least 2 weeks since prior surgery for initial or progressive disease and recovered - No concurrent surgery for brain cancer - At least 2 weeks since prior isotretinoin - At least 4 weeks since prior investigational agents

Additional Information

Official title Phase I/II Trial Of Imatinib Mesylate; (Gleevec; STI571) In Treatment Of Recurrent Oligodendroglioma And Mixed Oligoastrocytoma
Principal investigator Kurt Jaeckle
Description OBJECTIVES: 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. PHASE II: 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.
Trial information was received from ClinicalTrials.gov and was last updated in January 2013.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).