Phase II Trial of Bevacizumab Plus Erlotinib for Patients With Recurrent Malignant Glioma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- 6 Month Progression-free Survival
研究概览
简要总结
Primary objective:
To estimate 6-month progression free survival probability of pts w recurrent malignant gliomas treated w erlotinib + bevacizumab.
Secondary Objectives:
To evaluate safety & tolerability of erlotinib + bevacizumab among pts w recurrent malignant gliomas To evaluate radiographic response of pts w recurrent malignant gliomas treated w erlotinib + bevacizumab To evaluate pharmacokinetics of erlotinib when administered to pts w recurrent malignant gliomas; & to examine relationship of clinical response to Epidermal Growth Factor (EGFR) expression, amplification, & v-III mutation, phosphatase and tensin homolog (PTEN) expression, vascular endothelial growth factor (VEGF) expression, vascular endothelial growth factor receptor 2 (VEGFR-2) & phosphorylated protein kinase B (PKB/Akt) in archival tumor samples
详细描述
Exploratory, Phase II study designed to assess anti-tumor activity of combinatorial regimen consisting of erlotinib + bevacizumab among pts w recurrent malignant glioma. Signal transduction inhibitors, such as erlotinib, as well as anti-angiogenic agents, such as bevacizumab, are expected to exert a cytostatic anti-tumor effect. Primary endpoint of study is probability of progression-free survival at 6 months. An important secondary objective is to further assess the safety of erlotinib + bevacizumab for pts w RMG. Pharmacokinetic studies included in protocol will evaluate impact of enzyme-inducing anti-epileptic drugs (EIAEDs) on metabolism of erlotinib.
If study demonstrates that combo regimen of erlotinib + bevacizumab is associated w encouraging anti-tumor activity among pts w recurrent malignant glioma (RMG), further assessment of regimen in additional ph II & possibly ph III studies, will be considered.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 have histologically confirmed diagnosis of recurrent/progressive WHO gr III & IV MG & meet following inclusion criteria:
- •Age >18 yrs
- •Interval of >4 wks since prior surgery
- •Interval of >4 wks since prior external beam radiation therapy (XRT) or chemo, unless there is unequivocal evidence of progressive disease & pts have recovered from all anticipated toxicity of most recent therapy
- •Karnofsky performance status score >60
- •Hematocrit > 29 percent, absolute neutrophil count (ANC) >1,500 cells/microliter, platelets >100,000 cells/microliter
- •Serum creatinine <.5mg/dl, blood urea nitrogen (BUN) <25 mg/dl, serum glutamate oxaloacetate transaminase (SGOT) & bilirubin <1.5 x upper limit of normal (ULN)
- •For pts on corticosteroids, they have been on stable dose for 1 wk prior to entry
- •Pts have had prior bevacizumab are eligible however interval of >6 wks must have elapsed since their last dose
- •Signed informed consent approved by Institutional Review Board (IRB) prior to patient entry;
- •If sexually active, pts must agree to take contraceptive measures for duration of treatments
排除标准
- •Prior therapy w either bevacizumab/EGFR-directed agents
- •>3 prior recurrences
- •Pregnancy/breast feeding
- •Co-medication w immuno-suppressive agents other than corticosteroids including but not limited to cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil
- •Evidence of central nervous system (CNS) hemorrhage on baseline MRI on CT scan
- •Pts who require therapeutic anti-coagulation
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics & psychiatric illness/social situations that would limit compliance w study requirements, or disorders associated w significant immunocompromised state
- •Pts w another primary malignancy that has required treatment within past year
- •Pts w acute/chronic renal insufficiency/those w acute renal insufficiency of any severity due to hepato-renal syndrome/in peri-operative liver transplantation period
研究组 & 干预措施
Bevacizumab + Erlotinib
Bevacizumab + Erlotinib
干预措施: Bevacizumab and Erlotinib (Drug)
结局指标
主要结局
6 Month Progression-free Survival
时间窗: 6 months
The proportion of patients alive and progression free at 6 months
次要结局
- Radiographic Response(Patients were followed for the duration of the study, with a median follow-up of 103 weeks for grade III participants and 141.8 weeks for grade IV participants)
- Pharmacokinetics of Erlotinib: Cmax(Day 1 and 42 of Dosing Erlotinib)
- Pharmacokinetics of Erlotinib: AUC(Day 1 and 42 of Dosing Erlotinib)
- Association of Biomarkers and One-year Survival - Epidermal Growth Factor (EGFR)(1 year)
- Association of Biomarkers and One-year Survival - EGFR vIII(1 year)
- Association of Biomarkers and One-year Survival - Phosphatase and Tensin Homologue (PTEN)(1 year)
- Association of Biomarkers and One-year Survival - Phosphorylated Protein Kinase B (pAKT)(1 year)
- Association of Biomarkers and One-year Survival - Phosphorylated Mitogen-activated Protein Kinase (pMAPK)(1 year)
- Association of Biomarkers and One-year Survival - Vascular Endothelial Growth Factor (VEGF)(1 year)
- Association of Biomarkers and One-year Survival - VEGFR-2(1 year)