A Phase II Study of Intrathecal Topotecan (NSC #609699) in Patients With Refractory Meningeal Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 77
- 试验地点
- 1
- 主要终点
- Concentration of matrix metalloproteinases in the CSF
研究概览
简要总结
Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. This phase II trial is studying how well topotecan hydrochloride works in treating children with meningeal cancer that has not responded to previous treatment
详细描述
PRIMARY OBJECTIVES:
I. Determine the therapeutic activity of intrathecal topotecan, in terms of response rate and time to central nervous system (CNS) progression, in pediatric patients with recurrent or refractory neoplastic meningitis.
II. Determine the safety and toxicity of this regimen in these patients. III. Evaluate the concentration of matrix metalloproteinases (MMPs) in the cerebrospinal fluid (CSF) of these patients.
OUTLINE: Patients are stratified according to disease type (acute lymphoblastic leukemia vs. other leukemia/lymphoma vs medulloblastoma vs other solid tumors). (Recurrent CNS acute lymphoblastic leukemia stratum only open to accrual as of 11/30/04)
INDUCTION: Patients receive topotecan hydrochloride intrathecally (IT) over 5 minutes twice weekly for 6 weeks.
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
- •Histologically proven refractory leukemia, lymphoma, or other solid tumor thathas overt meningeal involvement (Recurrent CNS acute lymphoblastic leukemia stratum only open to accrual as of 11/30/04)
- •Definition of meningeal disease:
- •Leukemia/lymphoma (including acute lymphoblastic leukemia)
- •CSF cell count greater than 5/mm^3 AND evidence of blast cells oncytospin preparation or by cytology
- •Refractory to conventional therapy, including radiotherapy (i.e., in second or greater relapse)
- •No concurrent bone marrow relapse
- •Solid tumors (including medulloblastoma)
- •Presence of tumor cells on cytospin preparation or cytology OR presence ofmeningeal disease on MRI scans
- •No clinical evidence of obstructive hydrocephalus or compartmentalization ofCSF flow as documented by radioisotope indium In 111 or technetium Tc 99 DTPAflow study
- •If CSF flow block is demonstrated, focal radiotherapy must be administered tosite of block to restore flow and a repeat CSF flow study must show clearing of blockage
- •No ventriculoperitoneal or ventriculoatrial shunt unless:
- •Patient is shunt independent and there is evidence that the shunt is nonfunctional
- •CSF flow study demonstrates normal flow
- •No impending cord compression, CNS involvement requiring local radiotherapy(e.g., optic nerve), or isolated bulky ventricular or leptomeningeal basedlesions
- •Performance status - Lansky 50-100% (age 10 and under)
- •Performance status - Karnofsky 50-100% (over age 10)
- •At least 8 weeks
- •Platelet count greater than 40,000/mm^3 (transfusions allowed)
- •Bilirubin less than 2.0 mg/dL
- •SGPT less than 5 times normal
- •Creatinine less than 1.5 mg/dL
- •Electrolytes, calcium, and phosphorus normal
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No significant illness (e.g., uncontrolled infection, except HIV [i.e., AIDS-related lymphomatous meningitis])
- •Prior immunotherapy allowed and recovered
- •At least 3 weeks since systemic CNS directed chemotherapy (6 weeks for nitrosoureas) and recovered
- •At least 1 week since prior intrathecal (IT) chemotherapy (2 weeks for cytarabine [liposomal])
- •No prior IT chemotherapy on days -14 to -7 before study entry unless evidence of disease progression (e.g., increasing WBC and percentage blasts in patients with leukemia/lymphoma or increased leptomeningeal enhancements in patients with solid tumors) (Recurrent CNS acute lymphoblastic leukemia stratum only open to accrual as of 11/30/04)
- •Concurrent chemotherapy to control systemic disease or bulk CNS disease allowed if the systemic chemotherapy is not a phase I study agent that significantly penetrates the CSF (e.g., high-dose systemic methotrexate [greater than 1 g/m^2], thiotepa, high-dose cytarabine, temozolomide, IV mercaptopurine, nitrosourea, or topotecan) or an agent known to have serious unpredictable CNS side effects
- •Concurrent dexamethasone or prednisone allowed if part of a systemic chemotherapy regimen
- •See Disease Characteristics
- •At least 8 weeks since prior cranial irradiation and recovered
- •No concurrent whole brain or craniospinal irradiation
- •At least 7 days since prior investigational drug
- •Time period should be extended if patient has received any investigational agent that is known to have delayed toxic effects after 7 days or a prolonged half-life
- •No other concurrent investigational agents
- •No concurrent therapy (IT or systemic) for leptomeningeal disease
- •No other concurrent systemic agents that significantly penetrate the blood-brain barrier
排除标准
- 未提供
研究组 & 干预措施
Treatment (topotecan hydrochloride)
INDUCTION: Patients receive topotecan hydrochloride IT over 5 minutes twice weekly for 6 weeks.
CONSOLIDATION: Beginning 1 week after completion of induction, patients receive topotecan hydrochloride IT over 5 minutes weekly for 4 weeks in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Beginning 2 weeks after completion of consolidation, patients receive topotecan hydrochloride IT over 5 minutes twice monthly for 4 months and then monthly through year 1.
干预措施: topotecan hydrochloride (Drug)
Treatment (topotecan hydrochloride)
INDUCTION: Patients receive topotecan hydrochloride IT over 5 minutes twice weekly for 6 weeks.
CONSOLIDATION: Beginning 1 week after completion of induction, patients receive topotecan hydrochloride IT over 5 minutes weekly for 4 weeks in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Beginning 2 weeks after completion of consolidation, patients receive topotecan hydrochloride IT over 5 minutes twice monthly for 4 months and then monthly through year 1.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Concentration of matrix metalloproteinases in the CSF
时间窗: Up to 54 months
For the leukemia and lymphoma patients, an objective response rate, defined to be the proportion of Complete Responses of less than 0.10
时间窗: Up to 54 months
For the patients with solid tumors, a proportion of patients who do not experience an event, defined to be death, progressive disease, relapse, or second malignancy of less than 0.3
时间窗: Up to 54 months
Safety and toxicity
时间窗: Up to 54 months
次要结局
未报告次要终点