Ph I SU011248 + Irinotecan in Treatment of Pts w MG

Duke University

Status and phase

Completed

Phase 1

Conditions

Glioblastoma

Treatments

Drug: SU011248 & Irinotecan

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00611728

Pro00000931

Details and patient eligibility

About

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

Full description

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.

Enrollment

25 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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