A Phase I Study of the Cyclin-Dependent Kinase (CDK)/Protein Kinase C (PKC) Inhibitor UCN-01 (NSC 638850) in Combination With 5-Fluorouracil in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 试验地点
- 1
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. UCN-01 may increase the effectiveness of a chemotherapy drug by making tumor cells more sensitive to the drug.
PURPOSE: Phase I trial to study the effectiveness of fluorouracil plus UCN-01 in treating patients who have advanced or refractory solid tumors.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose, dose limiting toxicity, and toxicity profile of fluorouracil with UCN-01 in patients with advanced or refractory solid tumors.
- Assess the clinical pharmacokinetics of this regimen and correlate with observed toxicities in these patients.
- Obtain preliminary data on the therapeutic activity of this regimen in these patients.
OUTLINE: This is a dose escalation study of fluorouracil.
Patients receive fluorouracil IV over 24 hours on days 1, 8, 15, and 22. Patients receive an initial dose of UCN-01 IV over 72 hours beginning on day 2 during course 1 and then maintenance UCN-01 IV over 36 hours beginning on day 2 during subsequent courses. Treatment repeats every 4 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of fluorouracil until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 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 solid tumor that is refractory to standard therapy or for which no standard therapy exists
- •Measurable or evaluable disease
- •No CNS metastasis or primary CNS malignancy
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status:
- •Karnofsky 60-100%
- •Life expectancy:
- •Not specified
- •Hematopoietic:
- •WBC greater than 3,500/mm^3
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Bilirubin no greater than 1.5 mg/dL
- •SGOT and SGPT no greater than 2.5 times upper limit of normal
- •Creatinine no greater than 1.5 mg/dL OR
- •Creatinine clearance greater than 60 mL/min
- •Cardiovascular:
- •No history of coronary artery disease documented by prior myocardial infarction, angiography, or coronary-artery bypass grafting
- •No cardiac arrhythmias or congestive heart failure within the past 6 months
- •Stable atrial fibrillation on standard treatment allowed at discretion of investigator
- •DLCO at least 60% of predicted
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 2 months after study
- •No active serious or uncontrolled infection
- •HIV negative
- •No diabetes
- •No other medical condition that would preclude study
- •PRIOR CONCURRENT THERAPY:
- •See Disease Characteristics
- •Biologic therapy:
- •At least 4 weeks since prior immunotherapy and recovered
- •Chemotherapy:
- •At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered
- •Prior fluorouracil allowed
- •Endocrine therapy:
- •Not specified
- •Radiotherapy:
- •No prior mediastinal radiotherapy
- •At least 4 weeks since prior radiotherapy and recovered
- •Not specified
- •No concurrent anticonvulsant medications
排除标准
- 未提供