Ph I SU011248 + Irinotecan in Treatment of Pts w MG
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
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of SU011248 Plus Irinotecan in the Treatment of Patients With Malignant Glioma|
- Determine MTD & DLT of SU011248 + Irinotecan in pts w RMG not on EIAEDs [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Demographic & baseline characteristics [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
- Efficacy observations & measurements [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
- Safety observations & measurements [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
- PK measurements [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||March 2008|
|Study Completion Date:||September 2010|
|Primary Completion Date:||June 2010 (Final data collection date for primary outcome measure)|
Drug: SU011248 & Irinotecan
- Irinotecan-CPT 11-Camptosar
Sutent given in daily oral manner for 1st 4 wks of each 6wk cycle. You will not take any Sutent during last 14 days of each 6 wk cycle. CPT-11 will be given intravenously over 1 & 1/2 hrs on 1st day of each cycle & then again on days 14 & 28.
Sutent is approved for adult subjects w some forms of kidney cancer. It is considered "investigational" for brain tumors. Dosing will begin on day 1 of cycle 1 & continue daily for 4 wks by mouth.
Irinotecan is approved for adult subjects with some forms of colorectal cancer. It is also considered "investigational" for brain tumors. Irinotecan dose will depend on your height & weight. Irinotecan will be given intravenously over 90 min on days 1, 14 & 28 of 6wk cycle.
You will be seen in clinic approximately every 42 days for 1st 3 cycles of study drug, & then every other cycle thereafter. Your brain MRI examination will be done within 1 wk prior to completion of cycles 1-3, & then within 1 week prior to completion of every other cycle.
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.
|United States, North Carolina|
|Duke University Health System|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||David A. Reardon, MD||Duke University Health System|