A Phase I Study of Topotecan by Intracerebral Clysis for the Treatment of Recurrent Primary Malignant Brain Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Number of Participants With Dose Limiting Toxicities
研究概览
简要总结
This study will evaluate the safety and efficacy of a chemotherapeutic drug (topotecan) as it is given directly into brain tumors by a delivery technique called convection-enhanced delivery. This drug has been used for different types of cancer, but in this study it will be given by an experimental delivery technique designed to maximize the amount of drug delivered to the brain tumor and minimize the side effects in other parts of the body.
This study will also evaluate advanced magnetic resonance (MR) imaging techniques.
The study will assess quality of life parameters throughout the follow-up period.
详细描述
Clinical efficacy with chemotherapy has been discouraging for malignant brain tumors, mostly because of side effects and delivery limitations. Because they are locally invasive and rarely metastasize, malignant gliomas have features that make them uniquely amenable to new strategies of regional drug delivery. Intracerebral clysis (convection-enhanced delivery) is a novel drug delivery strategy that uses a microinfusion pump to establish a pressure gradient in the brain via implanted catheters. The pressure gradient produces convective forces that distribute a therapeutic agent throughout the tumor and surrounding brain tissue.
Non-invasive magnetic resonance imaging (MRI) methods of monitoring drug distribution and treatment response have been developed to maximize the clinical applications and minimize complications associated with treatment risks.
Study participants will be taken to the operating room to have 2 catheters surgically placed into their tumor and surrounding tumor bed. These catheters will then be connected to small infusion pumps which will slowly infuse topotecan continuously over 4-5 days. Patients will have daily MRI scans while in the hospital. Upon completion of the experimental treatment, patients will be discharged and will be followed up in the outpatient clinic.
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
- 1 Year 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with primary malignant brain tumor, or a newly diagnosed or recurrent malignant tumor of the brainstem. Patients with tumors of the brain must have been previously treated with external beam radiation. Patients with brainstem gliomas may or may not have been previously treated.
- •Patients with a tumor that is stereotactically accessible (MR scan must be obtained within 30 days of enrollment and must demonstrate an enhancing mass without significant mass effect. Tumors must be less than 100 cc in total volume).
- •Patients who demonstrate evidence of increasing contrast enhancement on MR or CT imaging while on stable or increasing dose of steroid.
- •Patients with a Karnofsky Performance Score of greater than or equal to
- •Men and women of child-bearing potential must practice birth control. Women of child bearing potential must have a negative serum or urine pregnancy test within 7 days of study entry.
- •Patients must possess the ability to give Informed Consent. Parent or guardian may give informed consent for minors.
- •Patients must be willing to and medically capable of undergoing the surgical operation.
- •Patients may not be receiving other investigational agents for the treatment of malignant astrocytoma.
- •There is no upper age limit. Patients at extreme upper end of the age spectrum will not be automatically excluded, but will be carefully scrutinized to determine their suitability for this procedure.
- •Patients must be at least 1 year old to participate in the study.
排除标准
- •Patients with diffuse subependymal or cerebrospinal fluid (CSF) disease.
- •Patients with tumors involving the cerebellum, or both hemispheres.
- •Patients with an active infection requiring treatment or having an unexplained febrile illness.
- •Patients who are known HIV positive or who are known positive for Hepatitis B or C virus
- •Patients who have received any form of radiation or chemotherapy within 4 weeks of protocol enrollment.
- •Patients with systemic diseases which may be associated with unacceptable anesthetic/operative risk.
- •Patients who have previously received systemic topotecan for their tumor
- •Patients less than 1 year of age
- •Patients who are not able to receive an MRI scan
研究组 & 干预措施
Topotecan
Once a plastic catheter is placed, within 24 hours of placement, the catheter will be connected to a small pump at the bedside, and the convection-enhanced delivery of the Topotecan will begin. The Topotecan will be infused for 4 to 5 days after which time the catheters will simply be pulled out. Patients will be monitored with blood tests and MRI scans during the treatment and at different time periods during the following months.
干预措施: Convection-Enhanced Delivery (Procedure)
Topotecan
Once a plastic catheter is placed, within 24 hours of placement, the catheter will be connected to a small pump at the bedside, and the convection-enhanced delivery of the Topotecan will begin. The Topotecan will be infused for 4 to 5 days after which time the catheters will simply be pulled out. Patients will be monitored with blood tests and MRI scans during the treatment and at different time periods during the following months.
干预措施: Topotecan (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities
时间窗: During treatment, up to 5 Days
Maximum Tolerated Dose (MTD)
时间窗: During treatment, up to 5 Days
If 2 participants within a cohort develop dose-limiting toxicity (DLT), the prior dose level is considered the maximum tolerated dose (MTD). Dose-Limiting Toxicities (DLT) will be defined as any new (or increased from baseline) treatment-related (drug and/or device) neurological deficits as exhibited on neurological examination with severity of grade 3 or higher.
次要结局
- Time to Tumor Progression/Recurrence(Treatment to progression, Up to 8 years)
- Time to Death(Treatment to Time of Death, Up to 8 Years)
研究者
Jeffrey N. Bruce
Edgar M. Housepian Professor of Neurological Surgery Research
Columbia University