Primary Objectives To determine maxi tolerated dose & dose limiting toxicity of SU011248 + Irinotecan in recurrent MG pts not on EIAEDs To characterize safety & tolerability of SU011248 + Irinotecan among pts w recurrent MG Secondary Objectives To evaluate pharmacokinetic profile of SU011248 & Irinotecan when co-administered in pts w MG To evaluate anti-tumor activity of SU011248 + Irinotecan

Primary interest for combining SU011248 w irinotecan in malignant glioma pts derives from dramatic anti-tumor activity recently demonstrated among RMG pts treated w humanized anti-VEGF monoclonal antibody, bevacizumab, when combined w irinotecan. 63 percent radiographic response rate was observed following treatment w regimen every other wk, & median progression-free survival was 23wks. Similar enhancement of chemo activity by VEGF-directed therapy w bev has been previously demonstrated for colorectal & lung cancer pts. SU011248 is being evaluated in current regimen because it may exert more potent anti-angiogenic effect than bev among MG pts due to its ability to inhibit PDGFR-mediated pericyte stabilization in tumor neovasculature.

Current proposed ph I study is designed to determine MTD & DLT of SU011248 when combo w irinotecan for pts w RMG. Both SU01148 & irinotecan are known to be metabolized by CYP3A4 cytochrome system. Current study will limit enrollment to pts who are not on CYP3A4-enzyme inducing anti-epileptic drugs.

Inclusion Criteria:

• Pts confirmed GBM, GS, AA, AO & AOA w recurrent disease following standard therapy consisting of at least external beam XRT & temo chemo
• Pts not had tumor biopsy <1 week/surgical resection <2 weeks prior to starting study drug
• Pts should be on non-increasing dose of steroids >7 days prior to obtaining baseline Gd-MRI of brain
• Age >18yrs
• KPS >70
• ANC >1.5 x 10 9/L
• Hgb >9 g/dL
• Platelets >100 x 10 9/L
• AST/SGOT & ALT/SGPT <2.5 x ULN
• Serum bilirubin <1.5 x ULN
• Serum CA <12 mg/dL
• Serum creatinine <1.5 x ULN/measured 24-hr CrCl>50mL/min/1.73m^2
• Pt has ability to understand & provide signed informed consent that fulfills IRB guidelines

Exclusion Criteria:

• Prior gr3/>toxicity/failure to CPT-11 therapy
• Prior Sunitinib malate therapy
• Concurrent administration of EIAEDs
• Major surgery <2 weeks of enrollment
• History of impaired cardiac function
• Other clinically significant cardiac diseases
• Uncontrolled diabetes
• Active/uncontrolled infection requiring intravenous antibiotics
• Impairment of GI function/GI disease that may significantly alter absorption of Sunitinib malate Sutent
• Acute/chronic liver/renal disease
• Cerebrovascular accident/transient ischemic attack <6mths of study enrollment
• Pulmonary embolism <6mths of study enrollment
• Pre-existing thyroid abnormality w thyroid function that can not be maintained in normal range w medication
• Pts taking warfarin sodium
• Pts have received chemo ≤4wks to starting study drug unless they have fully recovered from all anticipated side effects of such therapy
• Pts have received immunotherapy ≤2wks to starting study drug/have not recovered from side effects of such therapy
• Pts have received investigational drugs ≤2wks to starting study drug unless they have fully recovered from all anticipated side effects of such therapy
• Pts have received XRT ≤4wks to starting study drug unless they have fully recovered from all anticipated side effects of such therapy
• Pts have undergone major non-CNS surgery ≤2wks to starting study drug/pts who 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 who are pregnant/breast feeding/adults of reproductive potential not employing effective method of birth control
• Known diagnosis of HIV
• History of another primary malignancy that is currently clinically significant/currently requiring active intervention
• Pts unwilling to/unable to comply w protocol
• Existing intra-tumoral hemorrhage
• Concurrent participation in another clinical trial except for supportive care/non-treatment trials
• Other severe acute/chronic medical/psychiatric condition/lab abnormality that may increase risk associated w study participation/study drug administration/ may interfere w interpretation of study results, & in judgment of investigator would make subject inappropriate for entry into this study