Sarcosinamide Nitrosourea in Treating Patients With Metastatic or Unresectable Solid Tumors
A Phase I Trial of Sarcosinamide Nitrosourea (SarCNU) in Patients With Solid Tumors
研究概览
详细说明
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose (MTD) of an oral formulation of SarCNU given on an every 4th day times three schedule (days 1, 5, 9).
II. Establish an appropriate oral dose of SarCNU for phase II clinical trials. III. Identify the dose-limiting toxicities (DLTs) of SarCNU. IV. Determine the oral bioavailability of SarCNU. V. Characterize the plasma pharmacokinetics of SarCNU.
SECONDARY OBJECTIVES:
I. Determine whether SarCNU undergoes metabolic N-demethylation to generate reactive isocyanate species that have been implicated in BCNU pulmonary toxicity.
II. Evaluate response to treatment with SarCNU in patients with measurable or evaluable disease.
III. Attempt to establish pharmacodynamic relationships for response and/or toxicity.
OUTLINE: This is a dose-escalation study.
Patients receive oral sarcosinamide nitrosourea (SarCNU) on days 1, 5, and 9. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of SarCNU 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.
Patients are followed at 4-5 weeks posttreatment.
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
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Massachusetts
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Boston、Massachusetts、美国、02115
- Dana-Farber Cancer Institute
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Histologically documented malignancy, which is either metastatic or inoperable, for which there is no known curative or standard palliative therapy, or all standard therapeutic approaches have failed
- Patients with leukemia or primary CNS malignancies are excluded; patients with metastatic disease to the CNS, who are not receiving anticonvulsants, including phenytoin, carbamazepine, phenobarbital, primidone, and felbamate, and who have reasonable expectation of surviving long enough to receive two cycles of therapy, are eligible
- Life expectancy of 2 months or longer
- ECOG performance status of 0-2
- Pretreatment laboratory data, obtained within 14 days of study entry, must meet the following criteria:
- ANC >= 1,500 /mm^3
- Platelets >= 100,000 /mm^3
- SGOT =< 2.5-times upper limit of normal
- SGPT =< 2.5-times upper limit of normal
- Total bilirubin =< upper limit of normal
- Creatinine =< 1.5 mg/dl
- Creatinine CL >= 60 ml/min (measured 24hr) if creatinine > 1.5 mg/dl
- DLCO >= 80% predicted
- At least 4 weeks since last receiving radiotherapy or chemotherapy and complete recovery from previous treatment related toxicity
- No prior treatment with a nitrosourea or with bleomycin
- No enzyme inducing anticonvulsant agents
- At least 2 weeks since major surgery
- Patients must not have uncontrolled serious medical or psychiatric illness
- Women of childbearing potential must not be lactating or pregnant, because of the proven teratogenicity of other agents of this class; a negative pregnancy test has to be obtained within 2 weeks of entry; both fertile males and females must use adequate contraception upon entry into the study
- Patients must have given signed informed consent
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：Treatment (SarCNU)
Patients receive oral sarcosinamide nitrosourea (SarCNU) on days 1, 5, and 9. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SarCNU 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. |
相关研究
相关研究
其他名称：
Given PO
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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MTD
大体时间：28 days
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28 days
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Pharmacokinetics: plasma concentration-time profiles of SarCNU
大体时间：Days 1 and 9 of course 1: 5, 15, 20, 30, and 45 min; 1, 2, 3, 4, and 6 hr
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Analyzed by nonlinear least squares regression using WinNonlin (Scientific Consulting, Inc.).
Final values of the iterated parameters in the best-fit equations describing the plasma profiles will be used to calculate all pharmacokinetic terms according to standard equations.
Mean values of the pharmacokinetic parameters will be calculated at each dose and subject to appropriate statistical tests for the existence of dose-dependent trends.
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Days 1 and 9 of course 1: 5, 15, 20, 30, and 45 min; 1, 2, 3, 4, and 6 hr
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合作者和调查者
调查人员
- 首席研究员：Joseph Eder、Dana-Farber Cancer Institute
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- NCI-2013-00028
- U01CA062490 (美国 NIH 拨款/合同)
- 99-046
- CDR0000067290 (注册表标识符：PDQ (Physician Data Query))
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
在美国制造并从美国出口的产品
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