Ph I SU011248 + Irinotecan in Treatment of Pts w MG
- Conditions
- Glioblastoma
- Registration Number
- NCT00611728
- Lead Sponsor
- Duke University
- Brief 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
- Detailed 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 25
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method Determine MTD & DLT of SU011248 + Irinotecan in pts w RMG not on EIAEDs 6 months
- Secondary Outcome Measures
Name Time Method Efficacy observations & measurements 6 months Safety observations & measurements 6 months PK measurements 6 months Demographic & baseline characteristics 6 months
Trial Locations
- Locations (1)
Duke University Health System
🇺🇸Durham, North Carolina, United States