A Phase I/II Study of Intraoperative Radiotherapy for Patients With Large Brain Metastases Treated With Neurosurgical Resection
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events
研究概览
简要总结
The primary purpose of this study is to establish a maximum tolerated dose (MTD) through a dose-escalation trial using intraoperative radiotherapy (IORT) following neurosurgical resection for large brain metastases, and to determine the progression-free survival rate as in the recurrence rate of treated brain metastasis.
详细描述
The potential for delivering ablative doses of radiation to the tumor bed while simultaneously sparing normal brain parenchyma from significant doses of radiation and reducing the potential for tumor repopulation has led to interest in the use of intraoperative radiotherapy (IORT) for brain metastasis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Participants must be ≥ 18 years of age.
- •Participants must have a Karnosfky performance status of ≥ 50%.
- •Participants must not have had prior intracranial radiation.
- •Participants must have a life expectancy greater than 3 months.
- •Participants must have a preoperative MRI Brain T1-Gadolinum enhanced scan demonstrating a non-dural based lesion with greatest diameter ≥ 2.5 cm.
- •Sufficient distance (≥ 2cm) of the intracranial lesion from optic structures (optic chiasm and bilateral optic nerves) and brainstem to meet established normal structure dose limits.
- •Subject or subject's legal representative to provide signed/written informed consent to participate in the study protocol.
- •Surface of balloon applicator must be ≥ 1cm from skin overlying closest portion of calvarium.
- •Participants may remain on systemic therapy if they are receiving immunotherapy (anti-PD1, anti-PDL1, anti-CTLA-4), capecitabine, temozolomide, etoposide, vinorelbine, pemetrexed, lapatinib, traztuzumab, bevacizumab, mTor or ALK targeted agents with no break prior to initiating IORT.
- •9.1 Participants receiving cisplatin, methotrexate, taxanes, tyrosine kinase inhibitors, or BRAF targeted agents must have a seven day washout period prior to receiving IORT.
- •9.2 Participants receiving doxorubicin, T-DM1, or antibody-drug conjugates must have a fourteen day washout period prior to receiving IORT.
- •Participants receiving all other concurrent systemic agents will undergo consideration for a washout period prior to receiving IORT at the discretion of the study principal investigator.
排除标准
- •Participants may not be pregnant or breast-feeding.
- •Patients must not have dural lesions or leptomeningeal disease.
- •Patients must not have psychiatric or social conditions limiting adherence to protocol guidelines.
- •Patients must not have contraindications to anesthesia, surgery, or MR imaging with Gadolinium injection.
- •Patients must not have a frozen section diagnosis of small cell carcinoma, lymphoma, germinoma or non-malignant histology.
- •Patients with additional unresected brain metastases must have a limited number of lesions/or volume of intracranial disease amenable to stereotactic radiotherapy at the discretion of the study principal investigator.
- •Patients deemed to require postoperative whole brain radiotherapy should be excluded.
研究组 & 干预措施
Treatment Arm
intraoperative radiotherapy (IORT) arm
干预措施: intraoperative radiotherapy (IORT) (Radiation)
结局指标
主要结局
Number of Participants With Adverse Events
时间窗: 12 months
Number of adverse events reported per participant.
Established Maximum Tolerated Dose
时间窗: Phase I cohorts; 90 days from treatments
Maximum tolerated dose will be determined by classical 3+3 dose-escalation design. Toxicity will be measured using the National Cancer Institute Common terminology criteria for adverse events (version 5.0). The first dose of 18Gy will be administered to the first 3 subjects, after 90 days from treatment a safety assessment for dose limiting toxicities will be done to determine if the next 3 subject will escalation to dose of 21Gy or receive 18Gy. If escalation to 21Gy is permitted, then after 90 days from treatment a safety assessment for dose limiting toxicities will be done to determine if next cohort of 3 subjects will escalate to a dose of 24Gy or receive 21Gy. The highest dose level to be administered will be 24 Gy if permitted by safety assessments.
次要结局
未报告次要终点
研究者
Shiao Yuo Woo,M.D.
Principal Investigator
University of Louisville