Phase I Trial of 5-Fluoro-2'-Deoxycytidine With Tetrahydrouridine
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 58
- 试验地点
- 4
- 主要终点
- Maximum tolerated dose (MTD) of 5-fluoro-2-deoxycytidine (FdCyd) when given with tetrahydrouridine (THU) determined by dose-limiting toxicities
研究概览
简要总结
This phase I trial studies the side effects and best dose of 5-fluoro-2-deoxycytidine when given together with tetrahydrouridine in treating patients with solid tumors that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Drugs used in chemotherapy, such as 5-fluoro-2-deoxycytidine and tetrahydrouridine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of 5-fluoro-2'-deoxycytidine (5-fluoro-2-deoxycytidine) (FdCyd) administered by intravenous (IV) infusion over three hours with concomitant infusion of 350 mg/m2 of tetrahydrouridine (THU).
II. To describe the toxicities of FdCyd co-infused with THU.
III. To obtain preliminary evidence of anti-tumor activity in patients treated with this combination.
IV. To evaluate the pharmacokinetics of FdCyd and THU when co-infused.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Advanced, histologically-confirmed neoplastic disease refractory to standard therapy or for which no standard therapy exists
- •Karnofsky performance status of at least 60% and estimated survival of at least two months
- •Serum creatinine =< 2.0 mg/dl or creatinine clearance >= 50 ml/min
- •Absolute neutrophil count (ANC) >= 1,500/ul
- •Platelets >= 125,000/ul
- •Bilirubin =< 1.5 mg/dl
- •Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 3 times the upper limits of normal
- •Prior antineoplastic therapy must have been completed at least four weeks prior to the patient's entry on this study, or patients must have recovered from any expected side effects of the prior therapy; there is no limit on the number of cycles of prior chemotherapy
- •Patients must be ineligible for or have refused participation in higher priority institutional protocols
- •Written, voluntary, informed consent of the patient must be obtained in compliance with institutional, state and federal guidelines
- •Pregnant patients are INELIGIBLE; all patients of child-bearing potential, both male and female, must be advised to practice adequate contraception; premenopausal women must have a negative pregnancy test prior to entry on this study
- •Patients with any non-malignant intercurrent illness (e.g. cardiovascular, pulmonary, or central nervous system disease) which is either poorly controlled with currently available treatment, or which is of such severity that the investigators deem it inappropriate to treat the patient on this protocol are INELIGIBLE
- •Patients currently being treated for a severe infection or who are recovering from major surgery are INELIGIBLE until recovery is deemed complete by the investigators
- •The presence of measurable disease is NOT required for this phase I study; if bidimensionally measurable disease is present, baseline measurements of up to 3 indicator lesions should be made no earlier than four weeks prior to the first cycle of chemotherapy; pleural effusions, ascites and bone metastases are not considered measurable
- •Complete blood count (CBC), differential count, platelet count, and blood chemistries should be done no earlier than 72 hours prior to each cycle of chemotherapy
- •Pretreatment tests should be done no earlier than two weeks prior to the first cycle of chemotherapy
- •Priority for accrual will be given to patients with breast cancer due to the in vitro data suggesting potential activity for this disease
排除标准
- 未提供
研究组 & 干预措施
Treatment (5-fluoro-2-deoxycytidine, tetrahydrouridine)
Patients receive tetrahydrouridine PO on day 1; 5-fluoro-2-deoxycytidine PO on days 1 and 8; tetrahydrouridine IV over 3 hours on days 2-5, 8, and 9-12; and 5-fluoro-2-deoxycytidine IV over 3 hours on days 2-5 and 9-12 of course 1. For all subsequent courses, patients receive tetrahydrouridine IV over 3 hours and 5-fluoro-2-deoxycytidine IV over 3 hours on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: 5-Fluoro-2-Deoxycytidine (FdCyd) (Drug)
Treatment (5-fluoro-2-deoxycytidine, tetrahydrouridine)
Patients receive tetrahydrouridine PO on day 1; 5-fluoro-2-deoxycytidine PO on days 1 and 8; tetrahydrouridine IV over 3 hours on days 2-5, 8, and 9-12; and 5-fluoro-2-deoxycytidine IV over 3 hours on days 2-5 and 9-12 of course 1. For all subsequent courses, patients receive tetrahydrouridine IV over 3 hours and 5-fluoro-2-deoxycytidine IV over 3 hours on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (5-fluoro-2-deoxycytidine, tetrahydrouridine)
Patients receive tetrahydrouridine PO on day 1; 5-fluoro-2-deoxycytidine PO on days 1 and 8; tetrahydrouridine IV over 3 hours on days 2-5, 8, and 9-12; and 5-fluoro-2-deoxycytidine IV over 3 hours on days 2-5 and 9-12 of course 1. For all subsequent courses, patients receive tetrahydrouridine IV over 3 hours and 5-fluoro-2-deoxycytidine IV over 3 hours on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
Treatment (5-fluoro-2-deoxycytidine, tetrahydrouridine)
Patients receive tetrahydrouridine PO on day 1; 5-fluoro-2-deoxycytidine PO on days 1 and 8; tetrahydrouridine IV over 3 hours on days 2-5, 8, and 9-12; and 5-fluoro-2-deoxycytidine IV over 3 hours on days 2-5 and 9-12 of course 1. For all subsequent courses, patients receive tetrahydrouridine IV over 3 hours and 5-fluoro-2-deoxycytidine IV over 3 hours on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Tetrahydrouridine (THU) (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) of 5-fluoro-2-deoxycytidine (FdCyd) when given with tetrahydrouridine (THU) determined by dose-limiting toxicities
时间窗: 28 days
MTD is defined as the highest dose tested in which \< 33% of patients experienced dose limiting toxicity. The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by National Cancer Institute Common Toxicity Criteria version 2.0 and nadir or maximum values for the laboratory measures), time of onset (i.e., cycle number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by cycle.
Survival
时间窗: Time from registration to time of death due to any cause, assessed up to 13 years
Survival and time to failure will be summarized with Kaplan-Meier plots to describe the outcome of patients treated on this protocol.
Time to treatment failure
时间窗: Time from registration to the first observation of disease progression, death due to any cause, or early discontinuation of treatment, assessed up to 13 years
Survival and time to failure will be summarized with Kaplan-Meier plots to describe the outcome of patients treated on this protocol.
次要结局
未报告次要终点