Fractionated Stereotactic Radiosurgery With Concurrent Bevacizumab for Brain Metastases: A Phase I Dose-escalation Trial
试验速览
- 阶段
- 1 期
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose
研究概览
简要总结
The investigators propose a new treatment strategy of fractionated stereotactic radiosurgery with concurrent bevacizumab for brain metastases. This phase I dose-escalation study is to establish the feasibility of this strategy and find the recommended doses.
详细描述
For each group (two groups according to tumor size), the design proceeds with cohorts of three patients, with the first cohort treated at a starting dose. If none of the three patients in a cohort experiences a dose-limiting toxicity (DLT), the next cohort with three patients will be treated at the next higher dose level. If one of the first three patients experiences a dose-limiting toxicity, the next cohort will be treated at the same dose level. The dose escalation continues until at least two patients among a cohort of three to six patients experience DLTs and the maximum tolerated dose (MTD) will be the dose level just below. If the highest planned dose was achieved without two patients experiencing DLTs, the MTD will be that dose level.
The DLT is defined as grade 4 or above toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 within 4 months after stereotactic radiosurgery (SRS):
Grade 4 central nervous system necrosis (life-threatening consequences; urgent intervention indicated) Grade 4 sensory or motor neuropathy (life-threatening consequences; urgent intervention indicated) Grade 4 hemorrhage (life-threatening consequences; urgent intervention indicated) or Grade 4 thromboembolic event (life-threatening consequences such as pulmonary embolism, cerebrovascular event, arterial insufficiency; hemodynamic or neurologic instability; urgent intervention indicated) Grade 4 hypertension (life-threatening consequences such as malignant hypertension, transient or permanent neurologic deficit, hypertensive crisis; urgent intervention indicated)
Study treatment:
Fractionated stereotactic radiosurgery:
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Single arm dose-escalation
Fractionated stereotactic radiosurgery:
Group 1: tumors 1.5~2.5 cm in diameter Dose level 1: 21 Gy in 3 fractions Dose level 2: 24 Gy in 3 fractions Dose level 3: 27 Gy in 3 fractions Group 2: tumors 2.5~3.5 cm in diameter Dose level 1: 18 Gy in 3 fractions Dose level 2: 21 Gy in 3 fractions Dose level 3: 24 Gy in 3 fractions Three fractions will be given in one week with at least 1 day break.
Concurrent bevacizumab:
Bevacizumab 7.5 mg/kg will be given one day before the first fraction of radiosurgery and 2 weeks after the first dose of bevacizumab.
干预措施: Fractionated stereotactic radiosurgery (Radiation)
Single arm dose-escalation
Fractionated stereotactic radiosurgery:
Group 1: tumors 1.5~2.5 cm in diameter Dose level 1: 21 Gy in 3 fractions Dose level 2: 24 Gy in 3 fractions Dose level 3: 27 Gy in 3 fractions Group 2: tumors 2.5~3.5 cm in diameter Dose level 1: 18 Gy in 3 fractions Dose level 2: 21 Gy in 3 fractions Dose level 3: 24 Gy in 3 fractions Three fractions will be given in one week with at least 1 day break.
Concurrent bevacizumab:
Bevacizumab 7.5 mg/kg will be given one day before the first fraction of radiosurgery and 2 weeks after the first dose of bevacizumab.
干预措施: bevacizumab (Drug)
结局指标
主要结局
Maximum tolerated dose
时间窗: 4 months
The maximum tolerated dose of fractionated stereotactic radiosurgery with concurrent bevacizumab for brain metastases.
次要结局
- Response rate(4 months)
- Time to progression(4 months)
- The incidence of radiation-induced adverse effects(4 months)