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)
试验速览
- 阶段
- 早期 1 期
- 状态
- 撤回
- 发起方
- 主要终点
- Changes in the spatial distribution of intratumorally-administered topotecan at serial timepoints using three-dimensional image reconstruction, as determined by MRI scan
研究概览
简要总结
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.
详细描述
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
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Topotecan (<=8cc) (Drug)
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.
干预措施: Cleveland Multiport Catheter (Device)
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.
干预措施: Magnetic Resonance Imaging (MRI) (Diagnostic Test)
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.
干预措施: Topotecan (>8cc) (Drug)
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.
干预措施: Cleveland Multiport Catheter (Device)
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.
干预措施: Magnetic Resonance Imaging (MRI) (Diagnostic Test)
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.
干预措施: Cleveland Multiport Catheter (Device)
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.
干预措施: Magnetic Resonance Imaging (MRI) (Diagnostic Test)
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.
干预措施: Lower Does Topotecan (Drug)
结局指标
主要结局
Changes in the spatial distribution of intratumorally-administered topotecan at serial timepoints using three-dimensional image reconstruction, as determined by MRI scan
时间窗: 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
时间窗: 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
时间窗: Up to 12 months
Number of intra-operative catheter related complications
时间窗: Up to 12 months
Documentation of possible, probable, or definite catheter-related complications
Number of catheter related complications after catheter removal
时间窗: Up to 12 months
Documentation of possible, probable, or definite catheter-related complications
Changes in the spatial distribution of intratumorally-administered topotecan associated with changes in the infusion rate, as determined by MRI scan
时间窗: 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
时间窗: Up to 12 months
Number of post-operative catheter related complications
时间窗: Up to 12 months
Documentation of possible, probable, or definite catheter-related complications
Change in the spatial distribution of intratumorally-administered topotecan at serial timepoints using a gadolinium-based contrast agent, as determined by MRI scan
时间窗: Up to 12 months
次要结局
- Safety as measured by the common terminology criteria for adverse events (CTCAE)(Up to 12 months)
- Number of Participants with response as measured by the Response Assessment in Neuro-Oncology (RANO) Criteria(Up to 12 months)
研究者
Michael Vogelbaum, MD, PhD
Principal Investigator
Case Comprehensive Cancer Center