Safety Evaluation of a Combination of Brain Radiation Therapy and Bevacizumab (Avastin®) for Treatment of Brain Metastasis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 21
- 试验地点
- 6
- 主要终点
- The Maximal Tolerated dose (MTD)
研究概览
简要总结
This phase I pilot study aims to define the safety of a combined treatment of bevacizumab and whole brain radiation therapy for the treatment of patients with brain metastasis of solid tumors. If this therapeutic scheme confirms it's safety profile, the investigators can expect:
- first, to allow that all patients can receive bevacizumab for their advanced and/or metastatic cancer if necessary, even in case of brain metastasis.
- Secondly, if this trial confirm a synergic effect of the combination of angiogenesis inhibitors and brain radiotherapy for local control of brain metastasis, an improvement of the therapeutic results for these patients which have a poor hope of survival and for which none innovative approach is currently suggested.
Moreover, the investigators hope that the analysis of the different data of MRI evaluation - morphological and functional - will allow better definition of radiological evaluation of the therapeutic effect of angiogenesis inhibitors on brain metastasis.
详细描述
Brain metastasis remain a common complication of many solid tumors, occurring from 10 to 20% of patients with cancer, and the incidence may arise up to 20-40% in autopsy series. Despite the treatment, the patient outcome is poor and brain metastasis become a major cause of death from cancer.
Some recent studies showed an increase incidence of brain metastasis; several explanations are evocated:
- The increased efficacy of brain imaging in screening of brain metastasis.
- The relative longer life expectancy of cancer patients in correlation with more efficient therapies (new chemotherapy drugs, targeted therapies) for visceral and bone metastasis, but without effect on the risk of brain metastasis (sanctuary effect),
Therapeutic management of brain metastasis: standards of care and improvement strategies
For patients with a poor survival hope, the treatment is limited to best supportive care with a palliative intent. At the opposite, a specific treatment of brain metastasis must be proposed when a real benefit may be expected.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 < age < 70 man or woman
- •Patient with a cytologically or histologically proven primary solid tumor
- •With measurable and inoperable brain metastasis,
- •Without meningeal carcinomatosis ,
- •ECOG performance status ≤ 2,
- •No previous treatment with angiogenesis inhibitors less than 3 months before inclusion,
- •No chemotherapy and/or immunotherapy less than 3 weeks before treatment,
- •No contra-indication to bevacizumab,
- •No proteinuria with urine dipstick for proteinuria > 2+
- •Blood sample ≤ 7 days before inclusion:
- •Hemoglobin ≥ 10 G/100 ml
- •Neutrophils count ≥ 1500 /mm3
- •Platelets ≥ 100 000 /mm3
- •Normal coagulation test: INR ≤ 1,5 ET TCA ≤ 1,5 x LSN 7 days before inclusion
- •A written informed consent must be obtained.
排除标准
- •Haemorrhagic brain metastasis,
- •Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg). Patients with high initial blood pressure are eligible if entry criteria are met after initiation or adjustment of antihypertensive medication,
- •Prior brain radiation therapy
- •Concomitant anticoagulant treatment
- •Significant surgical procedure less than 28 days before inclusion (1 day if minor surgical act)
- •Significant cardio-vascular disease, eg:
- •Cerebral vascular thrombosis/haemorrhage or myocardial infarction <6 months
- •Congestive heart failure > 2 NYHA
- •Uncontrolled coronary disease
- •Prior venous and/or arterial thrombosis < 6 months before inclusion
- •Severe concurrent uncontrolled medical disease,
- •Any psychiatric disorder that might prevent the subject from completing the treatment or interfere with the interpretation of the study results,
- •Pregnancy or breast feeding
- •Individual deprived of liberty or placed under the authority of a tutor.
研究组 & 干预措施
Bevacizumab
first level dose : 5 mg/kg Second level dose : 10 mg/kg Third level dose : 15 mg/kg
干预措施: Bevacizumab (Drug)
结局指标
主要结局
The Maximal Tolerated dose (MTD)
时间窗: The MTD will be evaluated 6 weeks after the first administration ob bevacizumab
The primary objective is to determine the Maximal Tolerated Dose (MTD) of the combination of bevacizumab and whole brain radiation therapy for patients with brain metastases
次要结局
- Tumor regression(The first evaluation will be performed 2 weeks after the first injection, 6 weeks after the end of radiotherapy and each 3 months)