A Phase I Study of SU011248 Plus Irinotecan in the Treatment of Patients With Malignant Glioma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Determine MTD & DLT of SU011248 + Irinotecan in pts w RMG not on EIAEDs
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
排除标准
- •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
- •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
结局指标
主要结局
Determine MTD & DLT of SU011248 + Irinotecan in pts w RMG not on EIAEDs
时间窗: 6 months
次要结局
- Efficacy observations & measurements(6 months)
- Safety observations & measurements(6 months)
- PK measurements(6 months)
- Demographic & baseline characteristics(6 months)