Imatinib Mesylate in Treating Patients With Recurrent Meningioma

Study Overview
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Brief Summary
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Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have recurrent meningioma. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth

Detailed Description
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PRIMARY OBJECTIVE: I. Determine the efficacy of imatinib mesylate, in terms of 6-month progression-free survival, of patients with recurrent meningioma. SECONDARY OBJECTIVES I. Determine the response rate and overall survival of patients treated with this drug. II. Evaluate the safety profile of this drug in these patients. III. Determine the pharmacokinetics of this drug in these patients. IV. Develop exploratory data concerning surrogate markers of of angiogenic activity in vivo using functional neuro-imaging studies and in vitro assays of serum angiogenic peptides of this drug in these patients. V. Develop exploratory data concerning evidence of platelet-derived growth factor (PDGF) inhibition in tumor specimens taken from patients undergoing surgery VI. Develop exploratory data correlating molecular abnormalities in the tumor with response in patients treated with this drug. OUTLINE: This is a multicenter study. Patients are stratified according to concurrent use of enzyme-inducing antiepileptic drugs (yes vs no), histology (benign vs atypical or malignant), neurofibromatosis positivity (yes vs no), and preoperative candidacy (yes vs no). Patients receive oral imatinib mesylate once or twice daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months. PROJECTED ACCRUAL: A total of 60 patients (30 per stratum) will be accrued for this study within 8-12 months.

Official Title
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Phase II Trial of STI571 (NSC 716051) in Patients With Recurrent Meningioma

Conditions
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Adult Grade I Meningioma, Adult Grade II Meningioma, Adult Grade III Meningioma, Adult Meningeal Hemangiopericytoma, Adult Meningioma, Recurrent Adult Brain Tumor

Intervention / Treatment
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* Drug: imatinib mesylate
* Other: laboratory biomarker analysis
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed meningioma Benign, malignant, or atypical disease Neurofibromatosis (NF) type 1 or 2 allowed Hemangiopericytoma allowed Unequivocal evidence of tumor recurrence or progression by MRI or CT scan (on steroid dosage that is stable for at least 5 days) Evaluable residual disease by MRI or CT scan if previously treated with surgical resection for recurrent or progressive disease Newly diagnosed recurrent disease that requires surgical debulking allowed Prior standard external-beam radiotherapy, interstitial brachytherapy, or gamma-knife radiosurgery allowed provided disease has progressed since completion of therapy Patients who have had prior brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon positron-emission tomography or thallium scanning, magnetic resonance spectroscopy, or surgical documentation Patients with a history of NF may have other stable Central Nervous System (CNS) tumors (e.g., schwannoma, acoustic neuroma, or ependymoma) provided those lesions have been stable in size for the past 6 months Performance status - Karnofsky 60-100% More than 8 weeks Absolute neutrophil count at least 2,000/mm^3 Platelet count at least 120,000/mm^3 Hemoglobin at least 10 g/dL (transfusions allowed) No bleeding disorders Bilirubin less than 2 times upper limit of normal (ULN) Serum glutamic oxaloacetic transaminase (SGOT) less than 2 times ULN Prothrombin Time (PT), Partial thromboplastin time (PTT), and International normalized Ratio (INR) no greater than 1.5 times ULN Creatinine less than 1.5 mg/dL Creatinine clearance at least 60 mL/min No deep venous or arterial thrombosis within the past 6 weeks No pulmonary embolism within the past 6 weeks No serious active infection No prior intracranial hemorrhage No concurrent disease that would obscure toxicity or dangerously alter drug metabolism No other malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix unless the patient is in complete remission and off all therapy for that disease for at least 3 years No other significant medical illness that would preclude study participation Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception during and for 3 months after study participation At least 1 week since prior interferon or thalidomide No concurrent immunotherapy Concurrent epoetin alfa allowed At least 4 weeks since prior cytotoxic chemotherapy At least 2 weeks since prior vincristine At least 6 weeks since prior nitrosoureas At least 3 weeks since prior hydroxyurea or procarbazine No concurrent chemotherapy At least 1 week since prior tamoxifen No concurrent hormonal therapy At least 4 weeks since prior radiotherapy No concurrent radiotherapy Recovered from prior surgery Recovered from all prior therapy At least 1 week since prior noncytotoxic therapy (e.g., isotretinoin) except radiosensitizers At least 2 weeks since prior drugs that affect hepatic metabolism At least 4 weeks since prior investigational agents No concurrent warfarin (heparin or low-molecular weight heparin allowed) No other concurrent investigational agents No concurrent acetaminophen of more than 500 mg/day No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (imatinib mesylate)<br>Patients receive oral imatinib mesylate once or twice daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Other: pharmacological study/ laboratory biomarker analysis | Drug: imatinib mesylate<br>* Given orally<br>* Other names: Glivec;Other: laboratory biomarker analysis<br>* Correlative studies<br>Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 Months - Progression-free Survival According to Response Evaluation Using Macdonald Criteria | The Macdonald criteria, roughly similarly to other systems, divides response into 4 types of response based on imaging (magnetic resonance imaging [MRI]) and clinical features 1: complete response; 2: partial response; 3:stable disease; 4:progression Complete response imaging features: disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks; no new lesions clinical features; no corticosteroids; clinically stable or improved Partial response imaging features: 50% or more decrease of all measurable enhancing lesions sustained for at least 4 weeks: no new lesions clinical features: stable or reduced corticosteroids; clinically stable or improved Stable disease imaging features: does not qualify for complete response, partial response or progression clinical features: clinically stable Progression imaging features: 25% of more increase in enhancing lesions; any new lesions clinical features: clinical deterioration | At 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival According to Response Evaluation Using Macdonald Criteria | The Macdonald criteria, roughly similarly to other systems, divides response into 4 types of response based on imaging (MRI) and clinical features 1: complete response; 2: partial response; 3:stable disease; 4:progression Complete response imaging features: disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks; no new lesions clinical features; no corticosteroids; clinically stable or improved Partial response imaging features: 50% or more decrease of all measurable enhancing lesions sustained for at least 4 weeks: no new lesions clinical features: stable or reduced corticosteroids; clinically stable or improved Stable disease imaging features: does not qualify for complete response, partial response or progression clinical features: clinically stable Progression imaging features: 25% of more increase in enhancing lesions; any new lesions clinical features: clinical deterioration | 3 years | 
| Toxicity as Assessed by the Cancer Therapy Evaluation Program Common Toxicity Criteria (CTC) Version 2.0 | percentage of patients who had grade 3 or grade 4 adverse events | Up to 5 years after completion of study treatment | 
| Tumor Response as Assessed by MRI Using Macdonald Criteria | The Macdonald criteria, roughly similarly to other systems, divides response into 4 types of response based on imaging (MRI) and clinical features 1: complete response; 2: partial response; 3:stable disease; 4:progression Complete response imaging features: disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks; no new lesions clinical features; no corticosteroids; clinically stable or improved Partial response imaging features: 50% or more decrease of all measurable enhancing lesions sustained for at least 4 weeks: no new lesions clinical features: stable or reduced corticosteroids; clinically stable or improved Stable disease imaging features: does not qualify for complete response, partial response or progression clinical features: clinically stable Progression imaging features: 25% of more increase in enhancing lesions; any new lesions clinical features: clinical deterioration | Up to 5 years | 
| Concentration (Steady State) of Imatinib During Cycle One (Pharmacokinetics) | Blood collected before and at 1,2,4 ad 24 hours after ingestion of imatinib on day 8 of cycle 1 result is the measurement of the before dosing on day 8 (trough level) and the 24 hour dosing day 8 | pre dosing on day 8 and 24 hour dosing day 8 of Pre-dosing Day 9 | 
| Determine Survival for Patients Treated With Imatinib Mesylate | survival determined from start of treatment to date of death | 3 years |