Phase I Dose Escalation Trial of Hypofractionated Radiosurgery for Large Brain Metastasis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 4
- 主要终点
- Neurologic toxicity due to treatment, graded according to the CTCAE version 4.03
研究概览
简要总结
This phase I trial studies the side effects and best dose of hypofractionated radiosurgery in treating patients with large brain metastasis. Stereotactic radiosurgery can send x-rays directly to the tumor and cause less damage to normal tissue. Giving fractionated stereotactic radiosurgery may kill more tumor cells.
详细描述
PRIMARY OBJECTIVE:
To demonstrate the safety and feasibility of treating brain metastases or resection cavities greater than 3 cm with hypofractionated radiosurgery and to determine the maximum-tolerated radiation dose for hypofractionated radiosurgery (HR) delivered in 5 fractions, 2-3 fractions per week.
OUTLINE: This is a dose-escalation study.
Patients undergo hypofractionated stereotactic radiosurgery 2-3 times weekly (5 fractions total) for 2-3 weeks.
After completion of study treatment, patients are followed up at 1 month and then every 3 months thereafter.
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
- •Pathologic proven diagnosis of solid tumor malignancy
- •One brain metastasis or brain metastasis resection cavity with maximal diameter ≥ 3 cm (or ≥ 14 cc.) and ≤ 6 cm (or ≤ 113 cc.)
- •Recursive partitioning analysis (RPA) class I-II/ Karnofsky Performance status (KPS) ≥ 70%
排除标准
- •Prior stereotactic radiosurgery (SRS) to adjacent lesion such that planning target volume would have received more than 12 Gy
- •RPA class III (KPS < 70%)
- •Brain metastasis or resection cavity volume < 3 cm or > 6 cm
- •Radiosensitive or non-solid (eg. small cell lung carcinomas, germ cell tumors, leukemias, or lymphomas) or unknown tumor histologies
- •Concurrent chemotherapy (no chemotherapy starting 14 days before start of radiation)
- •Evidence of leptomeningeal disease by magnetic resonance imaging (MRI) and/or cerebrospinal fluid (CSF) cytology
- •Current pregnancy
- •More than 8 weeks between resection and radiosurgical procedure
- •Metastases to brain stem, midbrain, pons, or medulla or within 5 mm of the optic apparatus (optic nerves and chiasm)
- •Inability to undergo MRI evaluation for treatment planning and follow-up
研究组 & 干预措施
Hypofractionated Radiosurgery
HR (Hypofractionated Radiosurgery) delivered in 5 fractions, with a minimum of 2 and a maximum of 3 fractions being delivered per week, to patients with brain metastases or resection cavity greater than 3 cm and less than 6 cm.
Dose escalation will proceed according to the Escalation with Overdose Control (EWOC) method with a planned total enrollment of 24 patients, in 8 patient cohorts with 3 patients per cohort. A 4 month observation period will occur for each completed cohort prior to dose escalation, with a goal timeline for trial completion of 4 years from first patient enrollment.
干预措施: Hypofractionated Radiosurgery (Radiation)
结局指标
主要结局
Neurologic toxicity due to treatment, graded according to the CTCAE version 4.03
时间窗: Up to 2 years
Calculated with 95% CI.
Maximum tolerated dose (MTD) of hypofractionated radiosurgery defined as the highest dose level where a grade 3 or greater with an attribution score of ≥ 3 develops in ≤ 2 of 6 patients in a dose group
时间窗: 4 months
Graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. The rate of toxicities will be calculated with 95% confidence interval (CI).
次要结局
- Freedom from failure/progression free survival(Up to 2 years)
- Local control; lack of progression of disease in resection cavity as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria(4 months)
- Distant control: lack of progression of disease in surrounding brain as defined by RECIST criteria(4 months)
- Overall survival (OS): death from any cause(Up to 2 years)
- Long-term neurocognitive outcomes: using the Hopkins Verbal Learning Test-Revised (HVLT-R), Mini Mental Status Exam (MMSE) and Cognitive Functioning Subscale of the Medical Outcomes Scale (MOS)(Up to 2 years)
- Quality of life (QOL) outcomes: using the quality of life questionnaire for the Functional Assessment of Cancer Therapy-Brain (FACT-Br).(Up to 2 years)
研究者
Bree Eaton
Principal Investigator
Emory University