Study to Determine the Maximum Tolerated Time of Infusion for High-Dose Methotrexate, Administered as a Continuous Intravenous Infusion at a Dose of 6g/m² Per 24 Hours of Infusion Time
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 试验地点
- 41
- 主要终点
- Maximum tolerated infusion time for high-dose methotrexate
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as high-dose methotrexate work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Chemoprotective drugs, such as leucovorin calcium, may protect normal cells from the side effects of chemotherapy.
PURPOSE: This phase I trial is studying the side effects, best way to give, and best dose of high-dose methotrexate in treating patients with solid tumors.
详细描述
OBJECTIVES:
- To determine the maximum tolerated time to exposure to high-dose methotrexate when administered as a continuous infusion at a dose of 6 g/m² per 24 hours.
- To relate the methotrexate schedules investigated to the magnitude and duration of changes in plasma homocysteine and methionine.
- To relate evidence of the systemic effect of methotrexate through changes in plasma homocysteine and methionine to any hepatic, neurological, or antiproliferative toxicity observed in the study group.
OUTLINE: Patients receive a continuous infusion of high-dose methotrexate IV over 24, 30, 36, or 42 hours depending on time of study entry. Beginning at hour 42 or 48, patients receive leucovorin calcium IV every 6 hours for 3 days or until plasma methotrexate concentration is < 0.2 µM. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
Blood samples are collected at baseline and periodically during study and analyzed for pharmacodynamic effects on plasma homocysteine and methionine by gas chromatography/mass spectrometry techniques.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically proven malignancy, including but not limited to, any of the following:
- •Patients with MRI findings in keeping with a diffuse intrinsic pontine glioma will be eligible without histological confirmation of tumor type
- •Patients with a diagnosis of diffuse intrinsic pontine glioma who are not eligible for the erlotinib hydrochloride phase I study (CCLG-NAG-2005-09)
- •Patients with relapsed ependymoma following the CCLG phase II study of intravenous etoposide (CCLG-CNS-2001-4) or prior to this are eligible at the discretion of the physician
- •Patients with relapsed osteogenic sarcoma, other soft tissue sarcomas, or other solid tumors may be suitable for this study at the discretion of the physician
- •Radiologically evaluable disease without bone marrow involvement
- •PATIENT CHARACTERISTICS:
- •Inclusion criteria:
- •Lansky performance status (PS) 30-100% (for patients ≤ 12 years of age)
- •ECOG PS ≤ 2 (for patients ≥ 13 years of age)
- •Life expectancy ≥ 9 weeks
- •ANC > 1,000/mm³
- •Platelet count > 100,000/mm³
- •Hemoglobin > 9 g/dL
- •Serum creatinine ≤ 1.5 times upper limit of normal (ULN) for age
- •Serum total bilirubin normal
- •AST or ALT ≤ 2 times ULN
- •Glomerular filtration rate ≥ 60 mL/min
- •Negative pregnancy test
- •Fertile patients must use effective contraception
排除标准
- •Poor medical risk because of nonmalignant systemic disease or uncontrolled infection
- •Concurrent malignancies at other sites
- •PRIOR CONCURRENT THERAPY:
- •Inclusion criteria:
- •Prophylactic trimethoprim-sulfamethoxazole must be stopped 1 week prior to methotrexate administration
- •Exclusion criteria:
- •Received chemotherapy or biologic therapy within the past 4 weeks
- •Received radiotherapy within the past 6 weeks
结局指标
主要结局
Maximum tolerated infusion time for high-dose methotrexate
次要结局
- Plasma biochemical evidence of the systemic effect of methotrexate in terms of changes in plasma homocysteine and methionine