Avastin in Combination With Temozolomide for Unresectable or Multifocal Glioblastoma Multiformes and Gliosarcomas
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Response Rate
研究概览
简要总结
Primary objective- To determine efficacy of Avastin, 10 mg/kg every other week, in combination with standard 5-day temozolomide in terms of response rate.
Secondary objective- To determine safety of Avastin & Temozolomide in unresectable glioblastoma patients
详细描述
Subjects have histologically confirmed WHO gr IV primary malignant glioma that is unresectable/multifocal. This is Phase II study where up to 41 subjects will receive up to 4 cycles of Avastin & Temozolomide. Avastin administered at 10 mg/kg every 14 days beginning a minimum of 7 days after biopsy/28 days after craniotomy. Temozolomide dosed at 200 mg/m2 daily for 5 days in 28-day cycle. Patients will receive up to 4 cycles of Avastin & Temozolomide, then proceed with standard XRT. Study will use 2-stage "minimax" study design in which 21 subjects are accrued during 1st stage, with possibility that additional 20 patients accrued during 2nd stage. In initial Phase I & II trials, 4 potential Avastin-associated safety signals were identified: hypertension, proteinuria, thromboembolic events, & hemorrhage. Avastin-associated adverse events in Phase III trials include congestive heart failure, GI perforations, wound healing complications, & arterial thromboembolic events. Most common toxicity associated with Temozolomide has been mild myelosuppression.
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
- •Patients have histologically confirmed diagnosis of WHO gr IV primary malignant glioma. Patients will be unresectable or have multifocal disease.
- •Age ≥ 18years & life expectancy of >12 weeks
- •Evidence of measurable primary CNS neoplasm on contrast enhanced MRI.
- •Interval of <1 week between prior biopsy/4 weeks from surgical resection & enrollment on protocol
- •Karnofsky ≥60%
- •Hemoglobin ≥9g/dl, ANC ≥1,500 cells/microliter, platelets ≥125,000 cells/microliter
- •Serum creatinine ≤1.5 mg/dl, serum SGOT & bilirubin ≤1.5 x ULN
- •For patients on corticosteroids, they must have been on stable dose for 1 week prior to entry, if clinically possible, & dose should not be escalated over entry dose level
- •Signed informed consent approved by IRB prior to patient entry
- •No evidence of > grade 1 CNS hemorrhage on baseline MRI/CT scan
- •If sexually active, patients will take contraceptive measures for duration of treatments
排除标准
- •Pregnancy/breast feeding
- •Co-medication that may interfere with study results
- •Active infection requiring IV antibiotics
- •Prior or current Treatment w XRT/chemo for brain tumor, irrespective of grade of tumor
- •Evidence of > grade 1 CNS hemorrhage on baseline MRI or CT scan
- •Avastin-Specific Concerns:
- •Inadequately controlled hypertension
- •Any prior history of hypertensive crisis/hypertensive encephalopathy
- •New York Heart Association Grade II or > congestive heart failure
- •History of myocardial infarction/unstable angina < 6 months prior to study enrollment
- •History of stroke/transient ischemic attack < 6 months prior to study enrollment
- •Significant vascular disease
- •Symptomatic peripheral vascular disease
- •Evidence of bleeding diathesis/coagulopathy
- •Major surgical procedure, open biopsy,/significant traumatic injury within 28 days prior to study enrollment/anticipation of need for major surgical procedure during course of study
- •Core biopsy/other minor surgical procedure, excluding placement of vascular access device, <7 days prior to study enrollment
- •History of abdominal fistula, GI perforation, /intra-abdominal abscess <6 months prior to study enrollment
- •Serious, non-healing wound, ulcer, or bone fracture
- •Proteinuria at screening as demonstrated by either
- •UPC ratio ≥1.0 at screening OR
- •Urine dipstick for proteinuria ≥2+
- •Known hypersensitivity to any component of Avastin
- •Pregnant/lactating. Use of effective means of contraception in subjects of child-bearing potential
- •Current, ongoing treatment with full-dose warfarin or its equivalent
研究组 & 干预措施
Avastin and Temozolomide
Avastin administered at 10 mg/kg every 2 weeks beginning a minimum of 7 days after biopsy or 28 days after craniotomy. Temozolomide dosed at 200 mg/m2 daily for 5 days in a 28-day cycle.
干预措施: Avastin and Temozolomide (Drug)
结局指标
主要结局
Response Rate
时间窗: 4 months
The proportion of subjects with complete or partial response as determined by a modification of the RANO (Response Assessment in Neuro-Oncology) criteria. A confirmation of response was not required. Complete Response was defined as complete disappearance on MR/CT of all enhancing tumor and mass effect, off all corticosteroids (or receiving only adrenal replacement doses), accompanied by a stable or improving neurologic examination, and maintained for at least 4 weeks. Partial Response was defined as greater than or equal to 50% reduction in tumor size on MR/CT by bi-dimensional measurement, on a stable or decreasing dose of corticosteroids, accompanied by a stable or improving neurologic examination, and maintained for at least 4 weeks.
次要结局
未报告次要终点