Imatinib Mesylate, Vatalanib, and Hydroxyurea in Treating Patients With Recurrent or Relapsed Malignant Glioma

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant glioma
• Grade 3 or 4 disease
• In first, second, or third recurrence or relapse
• Multifocal disease allowed

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%
• Life expectancy ≥ 12 weeks
• Absolute neutrophil count > 1,500/mm^3
• Hemoglobin > 9 g/dL
• Platelet count > 100,000/mm^3
• Potassium normal*
• Total calcium (corrected) normal*
• Magnesium normal*
• Phosphorus normal*
• aspartate transaminase (AST) and alanine transaminase (ALT) < 2.5 times upper limit of normal (ULN)
• Bilirubin < 1.5 times ULN
• Negative proteinuria by dipstick OR total urinary protein ≤ 500 mg with creatinine clearance ≥ 50 mL/min by 24-hour urine collection
• 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 acute or chronic liver or renal disease
• left ventricular ejection fraction (LVEF) ≥ 45% by Multi Gated Acquisition Scan (MUGA) or echocardiogram
• No complete left bundle branch block
• No obligate use of a cardiac pacemaker
• No congenital long QT syndrome
• No history of or current ventricular or atrial tachyarrhythmias
• No clinically significant resting bradycardia (i.e., heart rate < 50 beats/minute)
• No right bundle branch block with left anterior hemiblock (bifascicular block)
• No uncontrolled hypertension ≥ grade 2, history of labile hypertension, or history of poor compliance with an antihypertensive regimen
• No concurrent unstable angina pectoris or angina pectoris within the past 3 months
• No congestive heart failure (CHF)
• No history of CHF or arrhythmias requiring concurrent digoxin or verapamil
• No acute myocardial infarction within the past 3 months
• No other impaired cardiac function or clinically significant cardiac disease
• No peripheral neuropathy ≥ grade 2
• No unresolved diarrhea ≥ grade 2
• No uncontrolled diabetes
• No active or uncontrolled infection requiring intravenous antibiotics
• No impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of vatalanib, hydroxyurea, and/or everolimus, including any of the following:
• Ulcerative disease
• Uncontrolled nausea, vomiting, or diarrhea
• Malabsorption syndrome
• Small bowel resection
• No other concurrent severe and/or uncontrolled medical condition that would preclude study participation or compliance
• No known HIV positivity
• No other primary malignancy that is clinically significant or requires active intervention NOTE: *Supplement allowed

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 2 weeks since prior tumor biopsy (4 weeks since prior surgical resection)
• Prior polifeprosan 20 with carmustine implant (Gliadel® wafer) allowed at discretion of principal investigator
• Prior hydroxyurea allowed
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and 1 week for metronomic-dosed chemotherapy [e.g., daily etoposide hydrochloride or cyclophosphamide]) and recovered
• More than 4 weeks since prior radiotherapy and recovered
• More than 2 weeks since prior immunotherapy and recovered
• More than 4 weeks since prior investigational drugs and recovered
• No prior platelet-derived growth factor- or vascular endothelial growth factor-directed therapies
• More than 2 weeks since prior hematopoietic colony-stimulating factor (e.g., filgrastim [G-CSF] or sargramostim [Granulocyte-macrophage colony-stimulating factor (GM-CSF)])
• Prior epoetin alfa allowed
• No concurrent warfarin