A Pilot Phase II Trial of Hypofractionated Intensity-Modulated Radiation Therapy (Hypo-IMRT) Combining With Temozolomide (TMZ) and Bevacizumab for Patients With Newly Diagnosed Glioblastoma Multiforme (GBM)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- 6-month Progression-free Survival
研究概览
简要总结
The purpose of this study is to find out whether Hypofractionated Intensity-Modulated Radiation Therapy (Hypo-IMRT) combining with temozolomide chemotherapy can be safely given with a targeted agent, bevacizumab, and how effective this study treatment will be in controlling your brain tumor.
详细描述
This is a pilot phase II trial of the combination of concurrent hypofractionated IMRT (60 Gy/2 weeks), temozolomide and bevacizumab followed by 6 cycles of adjuvant bevacizumab and temozolomide in patients with grade IV malignant gliomas (glioblastoma and gliosarcoma). The study will have survival and toxicity endpoints.
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
- •Histologically confirmed diagnosis of WHO grade IV primary malignant glioma (GBM or gliosarcoma).
- •Age ≥ 18 years at the time of study registration
- •Karnofsky Performance Scale ≥ 60%
- •Absolute Neutrophil Count (ANC) ≥ 1,500 cells/mm3, hemoglobin ≥ 9.0 g/dl, platelets ≥ 100,000 cells/ mm3
- •Serum creatinine ≤ 1.5 mg/dl, serum glutamate oxaloacetate transaminase (SGOT) and bilirubin ≤ 1.5 times upper limit of normal
- •Signed informed consent approved by the Institutional Review Board
- •Craniotomy or intracranial biopsy site must be adequately healed, free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of study entry. Study treatment should be initiated > 28 days following the last surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity)
排除标准
- •Life expectancy of less than 12 weeks
- •Prior treatment, including radiation therapy or chemotherapy, for GBM with the exception of surgery (Gliadel Wafers are allowed at the time of surgery)
- •Active malignancy, with the exception of superficial basal cell and/or superficial squamous (skin) cell, or carcinoma in situ of the cervix
- •Active infection requiring IV antibiotics
- •Pregnant or breast feeding
- •International normalized ratio (INR) > 1.5 and activated partial thromboplastin time (aPTT) > 1.5 × the upper limit of normal (ULN) (except for subjects receiving anticoagulation therapy) in the absence of therapeutic intent to anticoagulate the subject. Therapeutic anticoagulation is permitted
- •Evidence of ≥ Common Toxicity Criteria for Adverse Effects (CTCAE) v.3 grade 2 CNS hemorrhage (CNS hemorrhage when medical intervention indicated), but grade 1 CNS hemorrhage (asymptomatic radiographic findings on the baseline brain CT or MRI only) is allowed. Punctate hemorrhage or the presence of hemosiderin is not considered a Grade 1 event for the purpose of this study. )
- •Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg)
- •Prior history of hypertensive crisis or hypertensive encephalopathy
- •Current New York Heart Association (NYHA) Grade II or greater congestive heart failure
- •History of myocardial infarction or unstable angina within 6 months prior to enrollment
- •History of stroke or transient ischemic attack within 6 months prior to enrollment
- •Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to enrollment
- •History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month prior to enrollment
- •Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment or anticipation of need for major surgical procedure during the course of the study
- •Core needle biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to enrollment
- •History of abdominal fistula or gastrointestinal perforation within 6 months prior to enrollment
- •Serious, non-healing wound, active ulcer, or untreated bone fracture
- •Proteinuria as demonstrated by a Urine protein-creatinine ratios (UPC) ratio ≥ 1.0 at screening (Appendix A).
- •Known hypersensitivity to any component of bevacizumab
研究组 & 干预措施
RT with Temozolomide and Bevacizumab
Patients will be treated with hypofractionated IMRT (60 Gy in 10 Fx) and daily TMZ at 75 mg/m2 qd concurrent with IMRT (including weekends and holidays). Bevacizumab will be administered at 10 mg/kg on day 1 and day 15. Day 1 and the 1st Fx of IMRT must start on the same day. Four to six weeks following completion of concurrent IMRT, TMZ and bevacizumab therapy, patients will have a brain MRI and if there is no evidence of disease progression, patients will receive 6 cycles of Bevacizumab and TMZ. Beginning a minimum of 28 days after the last radiation treatment the bevacizumab will be dosed at 10 mg/kg on day 1 and day 15 of each cycle. TMZ will be given at 150-200 mg/m2 qd on days 1-5 of each cycle. Each cycle is 28 days.
干预措施: Bevacizumab (Drug)
RT with Temozolomide and Bevacizumab
Patients will be treated with hypofractionated IMRT (60 Gy in 10 Fx) and daily TMZ at 75 mg/m2 qd concurrent with IMRT (including weekends and holidays). Bevacizumab will be administered at 10 mg/kg on day 1 and day 15. Day 1 and the 1st Fx of IMRT must start on the same day. Four to six weeks following completion of concurrent IMRT, TMZ and bevacizumab therapy, patients will have a brain MRI and if there is no evidence of disease progression, patients will receive 6 cycles of Bevacizumab and TMZ. Beginning a minimum of 28 days after the last radiation treatment the bevacizumab will be dosed at 10 mg/kg on day 1 and day 15 of each cycle. TMZ will be given at 150-200 mg/m2 qd on days 1-5 of each cycle. Each cycle is 28 days.
干预措施: Temozolomide (Drug)
RT with Temozolomide and Bevacizumab
Patients will be treated with hypofractionated IMRT (60 Gy in 10 Fx) and daily TMZ at 75 mg/m2 qd concurrent with IMRT (including weekends and holidays). Bevacizumab will be administered at 10 mg/kg on day 1 and day 15. Day 1 and the 1st Fx of IMRT must start on the same day. Four to six weeks following completion of concurrent IMRT, TMZ and bevacizumab therapy, patients will have a brain MRI and if there is no evidence of disease progression, patients will receive 6 cycles of Bevacizumab and TMZ. Beginning a minimum of 28 days after the last radiation treatment the bevacizumab will be dosed at 10 mg/kg on day 1 and day 15 of each cycle. TMZ will be given at 150-200 mg/m2 qd on days 1-5 of each cycle. Each cycle is 28 days.
干预措施: RT (Radiation Therapy) (Radiation)
结局指标
主要结局
6-month Progression-free Survival
时间窗: 6 months
To use 6-month progression-free survival to assess the efficacy of the combination of hypofractionated IMRT delivering 60 Gy over 2 weeks with concurrent bevacizumab and temozolomide followed by 6 cycles of adjuvant bevacizumab and temozolomide.
次要结局
- Overall Survival, Measured From the Day of Initial Diagnosis (Biopsy or Surgery) to the Time of Death From Any Cause.(follow up for life)