Phase I Study of Methotrexate Infusion Into the Fourth Ventricle in Children With Recurrent Malignant Fourth Ventricular Brain Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of the direct administration of methotrexate into the fourth ventricle of the brain as determined by NCI's CTCAE
研究概览
简要总结
The goal of this clinical research study is to establish the maximum tolerated dose (MTD) of direct administration of methotrexate into the fourth ventricle of the brain in patients with recurrent malignant brain tumors including medulloblastoma, primitive neuroectodermal tumors (PNET), atypical teratoid/rhabdoid tumors (AT/RT), and ependymoma.
Methotrexate is designed to block cancer cells from dividing, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die.
详细描述
If the participant is eligible to take part in this study, the participant will have surgery to place a catheter into the ommaya reservoir. The ommaya reservoir is a catheter system that allows drugs to be administered directly to parts of the brain. This catheter will be used for the infusion of methotrexate directly into the 4th ventricle of the brain, which is 1 of the 4 connected fluid-filled cavities in the brain.
If the study doctor thinks it is necessary, based on the location of the tumor, the tumor may also be removed while the participant is already under anesthesia just before the catheter is placed.
Study Drug Administration:
The participant will receive 3 cycles of intraventricular methotrexate into the fourth ventricle. Each cycle will be of 4 weeks duration. During the first 3 weeks (Day 1-7 weekly) methotrexate will be infused twice weekly on days 1 and 4 (+/-2 days). The 4th week will be a rest week.
Methotrexate will be infused through the ommaya reservoir catheter directly into the 4th ventricle of the brain starting at a minimum of 7 days after the catheter placement surgery. A MRI will be done to confirm adequate cerebrospinal fluid flow. The infusion should last about 3 minutes each time.
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 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis: Patients with histologically verified medulloblastoma, primitive neuroectodermal tumor (PNET), atypical teratoid/rhabdoid tumor (AT/RT), ependymoma, or choroid plexus carcinoma with recurrence or progression involving the brain and /or spine. Patients with these tumors who did not present at diagnosis in the posterior fossa but have relapsed in the posterior fossa will be eligible. Patients who initially presented with disease in the posterior fossa but have now relapsed outside the posterior fossa will also be eligible.
- •Patient must have either measurable or evaluable tumor as assessed by MRI of the brain and total spine.
- •An implanted catheter in the fourth ventricle attached to an Ommaya reservoir or agreement to have one placed.
- •A minimum of 7 days between last dose of systemic chemotherapy and/or radiation therapy and first infusion of methotrexate into fourth ventricle.
- •Life expectancy of at least 12 weeks in the opinion of the PI.
- •Lansky score of 50 or greater if ≤16 years of age or Karnofsky score of 50 or greater if > 16 years of age.
- •Existing neurological deficits such as weakness, gait instability, cranial nerve deficits, or any other problems caused by the patient's disease or previous treatments must have been stable for a minimum of 1 week prior to study enrollment.
- •Patients must have recovered from the acute toxic effects of all prior anticancer chemotherapy.
- •Adequate bone marrow function defined by peripheral absolute neutrophil count (ANC) ≥ 500/ µL, platelet count ≥ 50,000/ µL(transfusion independent), and hemoglobin ≥ 9.0 gm/dL (may receive RBC transfusions)
- •Patient or patient's legal representative, parent (s), or guardian able to provide written informed consent.
排除标准
- •Enrolled in another treatment protocol
- •Has received another investigational or chemotherapy agent or radiation therapy with in 7 days prior to methotrexate infusion into the fourth ventricle
- •Evidence of untreated infection
- •Pregnant or lactating women
研究组 & 干预措施
Experimental
3 consecutive cycles of intraventricular methotrexate infusions into implanted fourth ventricle catheter/Ommaya reservoir following surgical catheter placement into fourth ventricle, each cycle will be of 4 weeks duration. During the first 3 weeks, methotrexate will be infused twice weekly on days 1 and 4 (+/- 2 days). The 4th week is a rest week.
干预措施: Ommaya Reservoir (Procedure)
Experimental
3 consecutive cycles of intraventricular methotrexate infusions into implanted fourth ventricle catheter/Ommaya reservoir following surgical catheter placement into fourth ventricle, each cycle will be of 4 weeks duration. During the first 3 weeks, methotrexate will be infused twice weekly on days 1 and 4 (+/- 2 days). The 4th week is a rest week.
干预措施: Methotrexate (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of the direct administration of methotrexate into the fourth ventricle of the brain as determined by NCI's CTCAE
时间窗: 3 months
Maximum Tolerated Dose (MTD) is determined using the criteria established by the National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events V4.0 (CTCAE).
次要结局
未报告次要终点
研究者
David Ilan Sandberg
Director of Pediatric Neurosurgery, Associate Professor, Departments of Pediatric Surgery and Neurosurgery UTHealth Medical School
The University of Texas Health Science Center, Houston