Hydroxyurea With or Without Imatinib Mesylate in Treating Patients With Recurrent or Progressive Meningioma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as hydroxyurea, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether hydroxyurea is more effective when given alone or together with imatinib mesylate in treating patients with meningioma. PURPOSE: This randomized phase II trial is studying how well hydroxyurea works compared with giving hydroxyurea together with imatinib mesylate in treating patients with recurrent or progressive meningioma.

Detailed Description
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OBJECTIVES: Primary Assess the progression-free survival of patients with recurrent or progressive meningiomas treated with hydroxyurea with vs without imatinib mesylate after surgery and radiotherapy. Secondary Determine the overall survival, and response rate of patients treated with this regimen. Determine the toxicity of this regimen in these patients. OUTLINE: This is a multicenter study. Patients are stratified according to WHO grade (I vs II-III). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral hydroxyurea twice daily and oral imatinib mesylate once daily in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive oral hydroxyurea twice daily in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed for up to 1 year.

Official Title
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IMATINIB Plus Hydroxyurea in the Treatment of Recurrent or Progressive Meningiomas: a Randomized Phase II Study

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: hydroxyurea
* Drug: imatinib mesylate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosed with meningioma WHO grade I-III Recurrent or progressive disease after prior surgery and radiotherapy, or radiosurgery Not amenable to further surgery No optic nerve sheet tumor and neurofibromatosis type II No known brain metastasis PATIENT CHARACTERISTICS: WHO performance status 0-2 ANC > 1,500/mm^3 Platelet count > 100,000/mm^3 Hemoglobin ≥ 9 mg/dL (transfusion allowed) Total bilirubin < 1.5 times upper limit of normal (ULN) SGOT and SGPT < 2.5 times ULN Creatinine < 1.5 times ULN Negative pregnancy test Fertile patients must use effective barrier method contraception during and for up to 3 months after completion of study therapy No second malignancy No known chronic liver disease (i.e., active hepatitis, cirrhosis) No known HIV infection No significant history of non-compliance to medical regimens or inability to grant reliable informed consent PRIOR CONCURRENT THERAPY: See Disease Characteristics No concurrent enzyme-inducing anti-epileptic drugs No concurrent therapeutic anticoagulation with warfarin (e.g., Coumadin®) Low-molecular weight heparin (e.g., Lovenox) or heparin allowed Mini-dose Coumadin® (e.g., 1 mg QD) allowed for prophylaxis of central venous catheter thrombosis, at the discretion of the treating physician No concurrent acetaminophen (Efferalgan®, Tachipirina®) allowed during imatinib mesylate administration No other concurrent anticancer agents, including chemotherapy or biological agents No other concurrent investigational drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral hydroxyurea twice daily and oral imatinib mesylate once daily in the absence of disease progression or unacceptable toxicity. | Drug: hydroxyurea<br>* Given orally<br>Drug: imatinib mesylate<br>* Given orally<br>|
| Experimental: Arm II<br>Patients receive oral hydroxyurea twice daily in the absence of disease progression or unacceptable toxicity. | Drug: hydroxyurea<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival, defined as ≥ 25% increase in tumor volume or new tumor on MRI |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  |  | 
| Response rate according to MacDonald criteria |  |  | 
| Toxicity as assessed by NCI CTCAE v. 3.0 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult grade I meningioma, adult grade II meningioma, adult anaplastic meningioma, adult papillary meningioma, recurrent adult brain tumor