Phase I/II Trial Of Repeated Super-selective Intraarterial Cerebral Infusion Of Bevacizumab Plus Carboplatin For Treatment Of Relapsed/Refractory Glioblastoma Multiforme And Anaplastic Astrocytoma
试验速览
- 阶段
- 1 期
- 状态
- 暂停
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Composite overall response rate
研究概览
简要总结
The high-grade malignant brain tumors, glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA), comprise the majority of all primary brain tumors in adults. This group of tumors also exhibits the most aggressive behavior, resulting in median overall survival durations of only 9-12 months for GBM, and 3-4 years for AA. Initial therapy consists of either surgical resection, external beam radiation or both. All patients experience a recurrence after first-line therapy, so improvements in both first-line and salvage therapy are critical to enhancing quality-of-life and prolonging survival. It is unknown if currently used intravenous (IV) therapies even cross the blood brain barrier (BBB). The investigators have shown in a previous phase I trial that a single Superselective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab (up to 15mg/kg) is safe and effective in the treatment of recurrent GBM. Therefore, this phase I/II clinical research trial is an extension of that trial in that the investigators seek to test the hypothesis that repeated dosing of intra-arterial Bevacizumab is safe and effective in the treatment of recurrent malignant glioma. Additionally the investigators will analyze if a combination with IA Carboplatin will further improve the treatment response. By achieving the aims of this study the investigators will also determine if IV therapy with Bevacizumab with IV Carboplatin should be combined with repeated selected intra-arterial Bevacizumab plus Carboplatin to improve progression free and overall survival. The investigators expect that this project will provide important information regarding the utility of repeated SIACI Bevacizumab therapy for malignant glioma, and may alter the way these drugs are delivered to the investigators patients in the near future.
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
- •18 years of age or older.
- •Documented histologic diagnosis of relapsed or refractory glioblastoma multiforme (GBM), anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma (AOA).
- •Circumscribed tumor recurrence with less than 3.5 cm greatest diameter
- •Patients with histologically confirmed low-grade brain tumor relapse with an enhancing tumor on MRI will be evaluated for toxicity only.
- •Patients must have at least one confirmed and evaluable tumor site.
- •Patients must have a Karnofsky performance status 70% (or the equivalent ECOG level of 0-2)
- •Patients must agree to use a medically effective method of contraception during and for a period of three months after the treatment period.
排除标准
- •Women who are pregnant or lactating.
- •Patients with significant intercurrent medical or psychiatric conditions that would place them at increased risk or affect their ability to receive or comply with treatment or post-treatment clinical monitoring.
- •Low GFR or history of hepatorenal syndrome
研究组 & 干预措施
Arm 2
Drug: Bevacizumab and Carboplatin
干预措施: Bevacizumab and Carboplatin (Drug)
Arm 1
Drug: Bevacizumab and Carboplatin
干预措施: Bevacizumab and Carboplatin (Drug)
结局指标
主要结局
Composite overall response rate
时间窗: 6 months
The composite overall response rate (CORR) will be examined. The overall response proportion along with a 95% confidence interval will be estimated via binomial proportions.
Six-month progression-free survival (PFS) and overall survival (OS)
时间窗: 2 years
PFS will be measured from the date of the first dose of SIACI Bevacizumab plus Carboplatin to the date of progression. OS will be measured from the date of the first dose of SIACI Bevacizumab plus Carboplatin to the date of death.
次要结局
- The safety of repeated SIACI of Mannitol, Bevacizumab plus Carboplatin at 15mg/kg and 150mg/m2 respectively.(1 month)
研究者
John Boockvar, MD Zucker SOM @Hofstra/Northwell
MD
Feinstein Institute for Medical Research
