Primary objective To determine maximum tolerated dose & dose limiting toxicity of imatinib mesylate & RAD001 when combined w fixed doses of hydroxyurea among pts w recurrent GBM who are on & not on enzyme-inducing anti-convulsants including pts not on anti-epileptic drugs Secondary objective To assess safety & tolerability of imatinib mesylate in combo w RAD001 & hydroxyurea in this population To characterize single-dose & repeated-dose pharmacokinetic profiles of imatinib mesylate & RAD001 combo therapy in this pt population.

To assess antiangiogenic effects, pre- and post-treatment, of imatinib mesylate, RAD001 & hydroxyurea combo therapy, using DCE-MRI to evaluate changes in extent of vascular permeability, perfusion & relative tumor blood volume; to explore assessment of tumor cellularity & tumor cell death by changes in DWI-MRI as quantitated by apparent diffusion coefficient maps.

This is open-label, single center, 1-arm ph I dose-escalation study of continuous, daily doses of imatinib mesylate & RAD001 administered orally in combination w fixed doses of hydroxyurea in adult pts w recurrent or relapsing glioblastoma multiforme. Study format includes classical "3+3" dose escalation design to determine MTD & DLT of imatinib mesylate + RAD001 when combined w hydroxyurea among GBM pts. Pts will be stratified based on whether they who are receiving EIACD & each stratum will independently dose escalate. Additionally, study will characterize safety, tolerability, biologic activity, & pharmacokinetic profile of this combo therapy.

Inclusion Criteria:

• Pts w confirmed GBM, GS, AA, AO & AOA are presenting in 1st, 2nd/3rd recurrence/relapse
• Pts without tumor biopsy <1 wk/surgical resection <2 wks prior to starting study drug
• For stratum of non-EIAED pts, each pts off all enzyme inducing anticonvulsants for >2 wks prior to starting study drug
• Pts should be on non-increasing dose of steroids for >7 days prior to obtaining baseline Gd-MRI of brain
• Pts should be on non-increasing dose of steroids for >7 days prior to starting study drug
• Pts w previous implantation of Gliadel may be eligible after discussion between investigator & sponsor
• Multifocal disease is eligible
• Age >18 yrs
• KPS >70
• Hematology: ANC>1.5 x 10^9/L, Hgb>9 g/dL, Platelets>100 x 10^9/L
• Biochemistry: K≥ LLN/correctable w supplement, Total Ca≥ LLN/correctable w supplement, Mg≥ LLN/correctable w supplement, P≥ LLN/correctable w supplement, AST/SGOT & ALT/SGPT <2.5 x ULN, Serum bilirubin <1.5 x ULN, Serum creatinine <1.5 x ULN/measured 24hr CrCl<0 mL/min/1.73m2, & Cholesterol≤ 00 mg/dL & triglyceride≤2.5 ULN
• Life expectancy ≥12wks
• Written informed consent obtained prior to any screening procedures

Exclusion Criteria:

• Pts w any peripheral neuropathy ≥CTCAE gr2
• Pts w unresolved diarrhea ≥CTCAE gr2
• History of impaired cardiac function
• Obligate use of cardiac pacemaker, Congenital long QT syndrome, History or presence of ventricular or atrial tachyarrhythmias, Clinically significant resting bradycardia , Right bundle branch block + left anterior hemiblock
• Other clinically significant cardiac diseases
• Uncontrolled Db
• Active or uncontrolled infection requiring intravenous antibiotics
• Impairment of GI function/GI disease that may significantly alter absorption of Gleevec, hydroxyurea and/or RAD001
• Acute/chronic liver/renal disease
• Other concurrent severe and/or uncontrolled medical condition that could cause unacceptable safety risks/compromise compliance w protocol
• Treatment w any hematopoietic colony-stimulating factor ≤2wks prior to starting study drug. Erythropoietin is allowed
• Pts w history of CHF/arrhythmias who are receiving treatment w digoxin/verapamil, & treatment cannot be discontinued/switched to different drug prior to starting study drug
• Pts taking warfarin sodium
• Pts received treatment w PDGF/mTOR directed therapies
• Pts received chemo ≤ 4wks prior to starting study drug/have not recovered from side effects of such therapy
• Pts received immunotherapy ≤2 wks prior to starting study drug/have not recovered from side effects of such therapy
• Pts received investigational drugs ≤4 wks prior to starting study drug/have not recovered from side effects of such therapy
• Pts received XRT ≤4 wks prior to starting study drug/have not recovered from side effects of such therapy
• Pts undergone major non-CNS surgery ≤2 wks prior to starting study drug/pts have not recovered from side effects of such therapy
• Cardiac pacemaker, Ferromagnetic metal implants other than those approved as safe for use in MR scanners, Claustrophobia, Obesity
• Female pts are pregnant/breast feeding,/adults of reproductive potential not employing effective method of birth control. Barrier contraceptives must be used throughout trial in both sexes. Oral, implantable/injectable contraceptives may be affected by cytochrome P450 interactions, & are therefore not considered effective for study. Women of childbearing potential have negative serum pregnancy test 48hrs prior to administration of Gleevec, hydroxyurea and/or RAD001.
• Known diagnosis of HIV infection
• Pts w history of another primary malignancy that is currently clinically significant/currently requires active intervention
• Pts unwilling to/unable to comply w protocol