Imatinib Mesylate and Hydroxyurea in Treating Patients With Recurrent or Progressive Meningioma

OBJECTIVES:

Primary

• Evaluate the activity of imatinib mesylate and hydroxyurea, as measured by 6-month progression-free survival, in patients with recurrent or progressive meningioma.

Secondary

• Evaluate the progression-free survival (PFS)
• Overall survival (OS),
• Objective response rate among patients treated with this regimen.

OUTLINE: This is an open-label study.

Patients receive oral imatinib mesylate once or twice daily and oral hydroxyurea twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 21 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed meningioma
• Recurrent or progressive disease after prior surgical resection
• Measurable disease by contrast-enhanced MRI
• Multifocal disease allowed
• No evidence of intratumor hemorrhage on pretreatment diagnostic imaging

• Stable postoperative grade 1 hemorrhage allowed
• No peripheral edema or central or systemic fluid collections ≥ grade 2 (e.g., pericardial effusion, pulmonary effusion, ascites)

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%
• Absolute neutrophil count > 1,500/mm³
• Hemoglobin > 9 g/dL
• Platelet count > 100,000/mm³
• Potassium normal*
• Calcium normal*
• Magnesium normal*
• Phosphorus normal*
• alanine aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times upper limit of normal (ULN)
• Bilirubin < 1.5 times ULN
• Creatinine < 1.5 times ULN OR creatinine clearance > 50 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No excessive risk of bleeding, as defined by stroke within the past 6 months
• No active systemic bleeding (i.e., gastrointestinal bleeding or gross hematuria)
• No history of central nervous system (CNS) or intraocular bleeding or septic endocarditis
• No concurrent severe and/or uncontrolled medical disease, including any of the following:

• Uncontrolled diabetes
• Congestive cardiac failure
• Myocardial infarction within the past 6 months
• Poorly controlled hypertension
• History of labile hypertension
• History of poor compliance with antihypertensive regimen
• Chronic renal disease
• Active uncontrolled infection requiring intravenous antibiotics
• No acute or chronic liver disease (i.e., hepatitis, cirrhosis)
• No HIV positivity
• No impairment of gastrointestinal function or disease that may significantly alter the absorption of imatinib mesylate, including any of the following:

• Ulcerative disease
• Uncontrolled nausea
• Vomiting
• Diarrhea
• Malabsorption syndrome
• Bowel obstruction
• Inability to swallow tablets
• No other malignancy within the past 5 years except basal cell skin cancer or cervical carcinoma in situ NOTE: *Unless correctable with supplements

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior therapy
• More than 1 week since prior tumor biopsy
• More than 2 weeks since prior surgical resection
• Prior hydroxyurea allowed provided patient has not had progressive disease or toxicity > grade 3
• No prior imatinib mesylate or other platelet-derived growth factor-directed therapy
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)*

• Chemotherapeutic agents such as etoposide that are normally given at shorter intervals allowed even if < 4 weeks from last prior dose of chemotherapy
• At least 4 weeks since prior radiotherapy*
• At least 1 week since prior biological, immunotherapeutic, or cytostatic drugs
• At least 2 weeks since prior investigational drugs
• No concurrent warfarin NOTE: *Unless there is unequivocal evidence of tumor progression