A Phase I Clinical Trial of Sequential Pralatrexate Followed by a 48-hour Infusion of 5- Fluorouracil Given Every Other Week in Adult Patients With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Recommended Dose of PDX Given With a Fixed Dose of 5-FU
研究概览
简要总结
RATIONALE: Pralatrexate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving pralatrexate together with fluorouracil may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of pralatrexate when given together with fluorouracil in treating patients with recurrent solid tumors
详细描述
PRIMARY OBJECTIVES:
I. To determine the recommended dose of PDX (pralatrexate) given in combination with a fixed dose of 5-FU (fluorouracil) administered as a 48-hour infusion given every other week.
SECONDARY OBJECTIVES:
I. To assess clinical response to therapy in subjects with measurable disease and time to disease progression in all subjects.
II. To assess the toxicity profile of the combination of PDX and 5-FU. III. To determine the pharmacokinetics of PDX and 5-FU and correlate with clinical toxicity.
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
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cancer patients who have failed standard therapy for their disease or for whom no such therapy is available are eligible, for which 5-fluoropyrimdines, including 5-FU, or inhibitors of DHFR (dihydrofolate reductase), including pralatrexate, have the potential for therapeutic benefit
- •Objectively measurable disease is preferred, but not required
- •Performance status of 0-2 (Eastern Cooperative Oncology Group [ECOG])
- •Prior treatment:
- •The patient should have recovered from the toxicities associated with prior chemotherapy (at least 3 weeks from prior therapy)
- •At least two or more weeks should have elapsed since any radiotherapy, and the patient should have recovered from the toxicity associated with such therapy
- •If a recent surgical procedure has been performed, the patient should have recovered from the surgery prior to entering this trial
- •Absolute granulocyte count of 1500 per mcL or greater
- •Platelet count of 100,000 per mcL or greater
- •Serum bilirubin less than 1.5 times the upper limits of the institutional normal
- •Serum creatinine less than the upper limits of normal
- •The patient must willingly give signed informed consent
排除标准
- •Pregnant women and nursing mothers are ineligible; eligible patients of reproductive potential should use adequate contraception if sexually active
- •Serious concurrent medical illness which would jeopardize the ability of the patient to receive the chemotherapy program outlined in this protocol with reasonable safety
- •Patients with active infections requiring intravenous antibiotic therapy are not eligible until the infection has resolved
- •Patients who are human immunodeficiency virus (HIV) antibody positive and are receiving highly active antiretroviral therapy (HAART) are ineligible
- •Concomitant administration of nonsteroidal anti-inflammatory drugs (NSAIDs) and trimethoprim/sulfamethoxazole will not be allowed
研究组 & 干预措施
Treatment (enzyme inhibitor therapy)
Patients receive pralatrexate IV over 5 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: pralatrexate (Drug)
Treatment (enzyme inhibitor therapy)
Patients receive pralatrexate IV over 5 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: fluorouracil (Drug)
Treatment (enzyme inhibitor therapy)
Patients receive pralatrexate IV over 5 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (enzyme inhibitor therapy)
Patients receive pralatrexate IV over 5 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: DNA analysis (Genetic)
Treatment (enzyme inhibitor therapy)
Patients receive pralatrexate IV over 5 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: high performance liquid chromatography (Other)
Treatment (enzyme inhibitor therapy)
Patients receive pralatrexate IV over 5 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: polymerase chain reaction (Genetic)
Treatment (enzyme inhibitor therapy)
Patients receive pralatrexate IV over 5 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: nucleic acid sequencing (Genetic)
Treatment (enzyme inhibitor therapy)
Patients receive pralatrexate IV over 5 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Treatment (enzyme inhibitor therapy)
Patients receive pralatrexate IV over 5 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacogenomic studies (Other)
Treatment (enzyme inhibitor therapy)
Patients receive pralatrexate IV over 5 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: polymorphism analysis (Genetic)
结局指标
主要结局
Recommended Dose of PDX Given With a Fixed Dose of 5-FU
时间窗: During the initial course (day 1 & 15 of a 4 week schedule)
Recommended dose of PDX given in combination with a fixed dose of 5-FU administered as a 48-hour infusion given every other weekMaximum tolerated dose will have been exceeded when 2 patients entered at a given dose level experience specified dose-limiting toxicities in the initial cycle
次要结局
- Number of Patients Experiencing Grade 3-4 Toxicity While Receiving the Combination of PDX and 5-FU(., "From the time the subject signs the consent form and ending 4 weeks following the final chemotherapy, an average of 3 years)
- Response to Therapy in Subjects With Measurable Disease(restaging imaging done after each two 4-week course until time of progression (the maximum duration of PFS = 588 days))
- Pharmacokinetics of PDX- AUClast(Pre-treatment, end of infusion, at 15, 30, and 60 min, and then at 2, 4, 6, 8, 12, 22, 23, 24, 45, and 46 hours for PDX.)
- 5-FU Plasma Levels(22, 23, 45 & 46 hours during the 48 hour infusion)
- Polymorphisms in Methylenetetrahydrofolate Reductase and Thymidylate Synthase(Prior to the first dose of protocol therapy)
- Time to Disease Progression(restaging imaging done after each two 4-week course until time of progression (longest time to progression = 588 days))