Intratumorally-Administered Topotecan Using CED in High Grade Glioma Undergoing Stereotactic Biopsy
2019年2月28日 更新者：Michael Vogelbaum, MD, PhD
Pilot Trial of Intratumorally-Administered Topotecan Using Convection-Enhanced Delivery (CED) in Patients With Suspected Recurrent/Progressive World Health Organization (WHO) Grade III or IV (High Grade) Glioma Undergoing Stereotactic Biopsy (IND 117,240)
The purpose of this study is to determine if treatment with topotecan by an alternative method, direct delivery into brain tumors, is safe and well tolerated. The Cleveland Multiport Catheter is a new, investigational device that will be used to deliver topotecan into your brain tumor. A second purpose of this study is to determine whether the Cleveland Multiport Catheter can be used effectively and safely to deliver topotecan into your brain tumor.
This study will also determine the best dose of topotecan to deliver to your tumor with use of the Cleveland Multiport Catheter and will also examine how your tumor responds to treatment with topotecan.
研究概览
地位
撤销
条件
详细说明
Primary Objectives
- To investigate by MR imaging the spatial and temporal distribution of topotecan in enhancing or nonenhancing bulk tumor administered by convection-enhanced delivery (CED) in patients with recurrent/progressive WHO grade III or IV (high grade) glioma (HGG) who have failed standard therapy comprising surgical biopsy and/or resection and adjuvant chemotherapy and radiotherapy.
- To investigate by MR imaging the influence of the rate and topotecan concentration, on the spatial and temporal distribution of topotecan administered by CED in patients with with recurrent/progressive HGG
Secondary Objectives
- To investigate the extent to which backflow may be observed on MRI during CEDmediated delivery of topotecan
- To assess the safety, tolerability and toxicity profile of topotecan administered by CED using different doses and infusion rates.
- To observe evidence of activity of single-agent topotecan administered by CED to patients with recurrent/progressive HGG who have failed standard therapy comprising surgical biopsy and/or resection and adjuvant chemotherapy and radiotherapy.
研究类型
介入性
阶段
- 第一阶段早期
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Histologically confirmed diagnosis of supratentorial WHO Grade III or IV Glioma (High Grade Glioma) that has undergone surgical biopsy or resection followed by adjuvant chemoradiotherapy, that has evidence of recurrence or progression based on imaging studies and a stereotactic biopsy is indicated for confirmation of recurrence/progression
- Karnofsky Performance Status 70-100
- MRI demonstration of a stereotactically accessible enhancing mass that does not require resection to relieve clinically significant mass effect
- Patient understands the procedures and agrees to comply with the study requirements by providing written informed consent
Laboratory values within the following ranges:
- Absolute neutrophil count (ANC) ≥ 1,500 / μL
- Platelet count ≥ 100,000 / μL
- Hemoglobin ≥ 10 g / dL
- prothrombin time (PT) / partial thromboplastin time (PTT) not above institutional norms
- Estimated glomerular filtration rate (eGFR) of at least 50 mL/min
Exclusion Criteria:
- Patient is mentally or legally incapacitated at the time of the study
- Known HIV(+) or has been diagnosed with AIDS
- Participation in another investigational drug study in the prior 4 weeks
- Positive pregnancy test in a female
- Patient, in the opinion of the investigator, is likely to be poorly compliant
- Diffuse subependymal or cerebrospinal fluid (CSF) disease
- Tumors involving the cerebellum
- Tumor enhancement involving both hemispheres
- Active infection requiring treatment
- Unexplained febrile illness
- Radiation or chemotherapy within 4 weeks of enrollment
- Systemic diseases associated with unacceptable anesthesia or operative risk
- Inability to undergo magnetic resonance imaging
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：非随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：Predominantly enhancing mass with volume of 8 cc or less
Only 1 Cleveland Multiport Catheter (CMC) will be placed and CED will be performed intra-operatively only in a magnetic resonance imaging (MRI) equipped Operating Room.
Topotecan infusion will be performed over a 4-hour period, with the goal of complete tumor coverage.
The initial rate will be 1.20 ml/hour and infusion will be monitored by intermittent MRI imaging.
The rate may be adjusted upwards during the infusion, in the event of incomplete tumor coverage, or downwards, if new mass effect is apparent.
Following completion of the 4-hour infusion, the CMC will be removed.
The initial rate for each subsequent patient may be adjusted upwards in increments of up to 1.20 ml/hour based upon the tumor coverage and safety characteristics of the previously treated patients.
|
In predominantly enhancing mass with a volume of 8 cc or less of topotecan administered
其他名称：
an investigational device, will be used to deliver the topotecan
to monitor the infusion of topotecan into the tumor
|
|
实验性的：Predominantly enhancing mass with volume of > 8 cc
2 Cleveland Multiport Catheter (CMCs) will be placed and the total infusion rate of Topotecan per CMC to be used for the first 24 hours for the first patient will be 0.834 ml/hour (3.48 microliters/minute/microcatheter).
The rate used for the second 24 hours of the infusion will be 1.668 ml/hour.
If the first patient does not experience rate-limiting toxicity, then the patient #2's initial infusion rate will start at the highest tolerated rate for patient #1, and the second 24-hour rate for that patient will be increased by 0.834 ml/hour.
Each subsequent patient will undergo rate escalation in a similar manner until we observe either: 1) complete coverage of the enhancing tumor by the infused Gadopentetic acid (Gd-DTPA), or 2) rate-limiting toxicity.
|
an investigational device, will be used to deliver the topotecan
to monitor the infusion of topotecan into the tumor
In predominantly enhancing mass with a volume of > 8 cc of topotecan administered.
Initial rate is 0.834ml/hour with an increase to 1.668 ml/hour at the second infusion
其他名称：
|
|
实验性的：Predominantly non-enhancing mass
The total infusion rate of Topotecan per Cleveland Multiport Catheter (CMC) to be used for the first 24 hours for the first patient will be 0.29 ml/hour.
The rate used for the second 24 hours of the infusion will be 0.58 ml/hour.
If the first patient does not experience rate-limiting toxicity, then the patient #2's initial infusion rate will start at the highest tolerated rate for patient #1, and the second 24-hour rate for that patient will be increased by 0.29 ml/hour.
Each subsequent patient will undergo rate escalation in a similar manner until we observe either: 1) complete coverage of the non-enhancing tumor by the infused Gd-DTPA, or 2) rate-limiting toxicity.
|
an investigational device, will be used to deliver the topotecan
to monitor the infusion of topotecan into the tumor
Rate for non-enhancing tumors has an initial dose of 0.29ml/hour
其他名称：
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Number of intra-operative catheter related complications
大体时间：Up to 12 months
|
Documentation of possible, probable, or definite catheter-related complications
|
Up to 12 months
|
|
Number of post-operative catheter related complications
大体时间：Up to 12 months
|
Documentation of possible, probable, or definite catheter-related complications
|
Up to 12 months
|
|
Number of catheter related complications after catheter removal
大体时间：Up to 12 months
|
Documentation of possible, probable, or definite catheter-related complications
|
Up to 12 months
|
|
Change in the spatial distribution of intratumorally-administered topotecan at serial timepoints using a gadolinium-based contrast agent, as determined by MRI scan
大体时间：Up to 12 months
|
Up to 12 months
|
|
|
Changes in the spatial distribution of intratumorally-administered topotecan associated with changes in the infusion rate, as determined by MRI scan
大体时间：Up to 12 months
|
Up to 12 months
|
|
|
Changes in the spatial distribution of intratumorally-administered topotecan at serial timepoints using volumetric magnetic resonance imaging, as determined by MRI scan
大体时间：Up to 12 months
|
Up to 12 months
|
|
|
Changes in the spatial distribution of intratumorally-administered topotecan at serial timepoints using three-dimensional image reconstruction, as determined by MRI scan
大体时间：Up to 12 months
|
Up to 12 months
|
|
|
Changes in the spatial distribution of intratumorally-administered topotecan associated with changes in the infusion concentration, as determined by MRI scan
大体时间：Up to 12 months
|
Up to 12 months
|
|
|
Changes in the spatial distribution of intratumorally-administered topotecan associated with changes in the infusion duration, as determined by MRI scan
大体时间：Up to 12 months
|
Up to 12 months
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Number of Participants with response as measured by the Response Assessment in Neuro-Oncology (RANO) Criteria
大体时间：Up to 12 months
|
Response includes objective response rate (ORR), median progression-free survival (PFS), proportion progression-free at six months (PFS-6), and median overall survival (OS)
|
Up to 12 months
|
|
Safety as measured by the common terminology criteria for adverse events (CTCAE)
大体时间：Up to 12 months
|
Safety will be determined through adverse events by arm
|
Up to 12 months
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Michael A. Vogelbaum, MD, PhD、Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2017年11月3日
初级完成 (实际的)
2018年11月19日
研究完成 (实际的)
2018年11月19日
研究注册日期
首次提交
2017年6月13日
首先提交符合 QC 标准的
2017年6月17日
首次发布 (实际的)
2017年6月20日
研究记录更新
最后更新发布 (实际的)
2019年3月1日
上次提交的符合 QC 标准的更新
2019年2月28日
最后验证
2019年2月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
Topotecan (<=8cc)的临床试验
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