Phase I Study of Intrathecal Spartaject-Busulfan in Patients With Neoplastic Meningitis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving drugs into the thin space between the lining of the spinal cord and brain may kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of intrathecal busulfan in treating patients with recurrent, refractory, or metastatic leptomeningeal tumors.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of intrathecal busulfan by a limited escalation dosage schedule in patients with recurrent or refractory leptomeningeal tumors.
- Determine the cerebrospinal fluid and serum pharmacokinetics of busulfan administered via intralumbar or intraventricular routes in these patients.
OUTLINE: This is dose-escalation study.
Patients receive intrathecal busulfan via intralumbar or intraventricular routes twice a week for 2 weeks (4 treatments). Any patient with objective or significant clinical response may continue treatment by receiving the same dose once a week for 2 consecutive weeks, once a week every other week for 3 weeks (2 treatments), and then once a month thereafter until disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of intrathecal busulfan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
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
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed neoplasm that is metastatic in the cerebrospinal fluid or leptomeningeal/subarachnoid space
- •Cytologic diagnosis of malignancy in the cerebrospinal fluid or neuroimaging evidence of leptomeningeal tumor by MRI
- •Must have a recurrent or refractory leptomeningeal tumor
- •Leptomeningeal tumors of leukemia, lymphoma, and all germ cell tumors must have also failed initial treatment or be recurrent
- •No evidence of obstructive hydrocephalus or complete block of the spinal cerebrospinal fluid pathways on prestudy technetium Tc 99m albumin or indium In 111 DTPA flow study
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status:
- •Karnofsky 60-100%
- •Life expectancy:
- •At least 8 weeks
- •Hematopoietic:
- •Absolute neutrophil count greater than 1,500/mm^3
- •Platelet count greater than 100,000/mm^3
- •Bilirubin less than 2.5 mg/dL
- •SGOT or SGPT less than 1.5 times normal
- •BUN less than 30 mg/dL
- •Creatinine less than 1.5 mg/dL
- •Calcium within normal limits
- •Neurological:
- •Neurological examination stable
- •No rapidly progressing or deteriorating neurological deficits
- •No active infectious process
- •Magnesium, phosphorus, potassium, chloride, and bicarbonate normal
- •Not pregnant or nursing
- •Fertile patients must use effective contraception
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •At least 4 weeks since prior immunotherapy
- •Chemotherapy:
- •At least 6 weeks since prior nitrosoureas or mitomycin
- •At least 4 weeks since any other prior chemotherapy
- •At least 3 weeks since prior intrathecal chemotherapy
- •No other concurrent intrathecal chemotherapy
- •Endocrine therapy:
- •For patients on corticosteroids:
- •Must be on a stable dose of corticosteroids for at least 1 week
- •Radiotherapy:
- •At least 3 weeks since prior radiotherapy to the CNS
- •At least 4 weeks since any other prior radiotherapy
- •No concurrent radiotherapy to the CNS
- •At least 3 weeks since prior surgery
- •No concurrent medication that may interfere with study results (e.g., immunosuppressive agents other than corticosteroids)
排除标准
- 未提供