ph i su011248 + irinotecan in treatment of pts w mg

Conditions: Glioblastoma

Summary: 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.

Eligibility criteria:
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 \ 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

Keywords: glioblastoma cpt 11 sutent sunitinib sunitinib malate malignant glioma gbm irinotecan camptosar anaplastic astrocytoma anaplastic oligodendroglioma anaplastic oligoastrocytoma su011248 brain tumor recurrent malignant glioma