Phase II Study of Bevacizumab Plus Either Temozolomide or Etoposide for (GBM) Patients Who Have Failed Bevacizumab Plus Irinotecan
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- The Primary Outcome Measure is 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 GBM treated w bev + either daily temozolomide/etoposide following progression on bev + irinotecan Secondary Objectives To evaluate safety & tolerability of bev + either daily temozolomide/etoposide among pts w recurrent GBM who have progressed on bev + irinotecan To evaluate radiographic response, progression free survival & overall survival of pts w recurrent GBM treated w bev + either daily temozolomide/etoposide following progression on bev + irinotecan
详细描述
This is exploratory, two-arm, phase II study designed to assess anti-tumor activity of bev + either daily temozolomide/etoposide among GBM pts w progressive disease following bev + irinotecan. About 48 participants w recurrent GBM will take part in this study. Approximately 24 participants will receive bev plus temozolomide & approximately 24 will receive bev + etoposide. Pts must have confirmed diagnosis of GBM & radiographic evidence of recurrence following prior therapy bev + irinotecan. 24 pts will be enrolled onto each arm of this single-stage study. If 4 or more of these 24 pts live 6/more months without disease progression, treatment regimen will be considered worthy of further investigation. Otherwise, treatment regimen will be determined not worthy of further investigation within pt population. Type I & II error rates associated w testing are 0.030 & 0.115 respectively. Management guidelines dose reduction/interruption for temo, etoposide, & bev.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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 confirmed diagnosis of GBM & radiographic evidence of recurrence following prior therapy w bev + irinotecan
- •Age >18 yrs
- •Interval of >4 wks between prior surgical resection/1 week from stereotactic biopsy
- •Interval of >12 wks from end of prior external beam radiation therapy (XRT) unless there is new area of enhancement consistent w recurrent tumor outside of XRT field,/there are progressive changes on MRI on >2 consecutive MRI scans >4wks apart, /there is biopsy-proven tumor progression
- •Interval of >4 wks from prior chemo / investigational agent unless pt has recovered from all anticipated toxicities associated w that therapy.
- •Eastern Cooperative Oncology Group (ECOG) 0-1
- •Hematocrit >29percent, absolute neutrophil count (ANC)>1,000 cells/ml l, platelets > 100,000 cells/ml l
- •Serum creatinine<1.5 mg/dl, serum glutamate oxaloacetate transaminase (SGOT) & bilirubin<1.5 times upper limit of normal (ULN)
- •Signed informed consent approved by Institutional Review Board (IRB) prior to pt entry
- •No evidence of hemorrhage on baseline MRI/CT scan other than those that are stable gr1
- •If sexually active, pts will take contraceptive measures for duration of treatments
排除标准
- •Co-medication that may interfere w study results
- •Active infection requiring intravenous antibiotics
- •Progression to daily etoposide/progression to daily temo
- •Gr3/greater toxicity related to prior bev therapy,/prior temozolomide/etoposide
- •Requires therapeutic anti-coagulation with warfarin.
- •Inability to comply w study and/or follow-up procedures
- •Current, recent,/planned participation in experimental drug study other than Genentech-sponsored bev cancer study
- •Inadequately controlled hypertension
- •Any prior history of hypertensive crisis/hypertensive encephalopathy
- •New York Heart Association (NYHA) Gr II/greater congestive heart failure
- •History of myocardial infarction (MI)/unstable angina within 6 mths prior to study enrollment
- •History of stroke/transient ischemic attack within 6 mths prior to study enrollment
- •Significant vascular disease
- •Symptomatic peripheral vascular disease
- •Evidence of bleeding diathesis or coagulopathy
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
- •Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
- •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
- •Serious, non-healing wound, ulcer, or bone fracture
- •Proteinuria at screening as demonstrated by either:
- •urine protein:creatinine (UPC) ratio >1.0 at screening /
- •Urine dipstick for proteinuria ≥ 2+
- •Known hypersensitivity to any component of bevacizumab
- •Pregnant or lactating. Use of effective means of contraception in subjects of child-bearing potential
研究组 & 干预措施
Temo + Avastin
Patients treated with bevacizumab + temozolomide
干预措施: Temo + Avastin (Drug)
VP-16 + Avastin
Patients treated with bevacizumab and VP-16 (etoposide)
干预措施: VP-16 + Avastin (Drug)
结局指标
主要结局
The Primary Outcome Measure is 6 Month Progression-free Survival.
时间窗: 6 months
Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or to death due to any cause.
次要结局
- Radiographic Response(41 months)
- Median Progression-free Survival (PFS)(41 months)
- Median Overall Survival (OS)(41 months)
- Grade 3 or Greater, Treatment Related, Non-hematologic Toxicities.(41 months)