A Phase I Pharmacologic Trial Of Infusional UCN-01 Given With A Weekly Schedule Of 5-Fluorouracil And Leucovorin
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 试验地点
- 2
研究概览
简要总结
RATIONALE: UCN-01 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining UCN-01 with chemotherapy may kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of combining UCN-01, fluorouracil, and leucovorin in treating patients who have metastatic or unresectable solid tumors.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of fluorouracil when given in combination with UCN-01 and leucovorin calcium in patients with metastatic or unresectable solid tumors.
- Determine the clinical toxic effects of this regimen in these patients.
- Determine the pharmacokinetics of these drugs in these patients.
- Correlate, if possible, the pharmacokinetics of these drugs with clinical toxicity in these patients.
- Assess the pharmacodynamic effects of these drugs in these patients.
- Assess any clinical activity of this regimen in patients with measurable disease.
OUTLINE: This is a dose-escalation study of fluorouracil (5-FU).
Patients receive leucovorin calcium (CF) IV over 2 hours and 5-FU IV (at the midpoint of CF administration) on day 1, followed by UCN-01 IV over 36-72 hours, on weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of 5-FU until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The recommended phase II dose (RPIID) is defined as the dose preceding the MTD. At least 6 additional patients are treated at the RPIID.
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 metastatic or unresectable and for which no standard curative or palliative measures exist or are effective
- •No brain metastases or primary CNS malignancy
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status
- •Life expectancy
- •Not specified
- •Hematopoietic
- •Absolute neutrophil count at least 1,500/mm3
- •Platelet count at least 100,000/mm3
- •Bilirubin no greater than 1.5 mg/dL
- •AST and ALT no greater than 3 times upper limit of normal
- •Creatinine no greater than 1.5 mg/dL OR
- •Creatinine clearance at least 60 mL/min
- •Cardiovascular
- •No known active coronary artery disease
- •No pulmonary dysfunction
- •HIV negative
- •No history of unusually severe and/or prolonged toxicity during prior therapy with fluorouracil (5-FU) or 5-FU prodrugs
- •No diabetes mellitus requiring insulin or oral hypoglycemic therapy
- •No ongoing or active infection requiring IV antibiotics
- •No other serious concurrent medical illness that would preclude study
- •No psychiatric illness or social situations that would preclude study
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •At least 4 weeks since prior immunotherapy and recovered
- •No concurrent cytokines during the first course of therapy
- •Chemotherapy
- •At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- •Endocrine therapy
- •No concurrent systemic corticosteroids
- •Radiotherapy
- •At least 2 weeks since prior radiotherapy and recovered
- •No prior pulmonary or mediastinal radiation exceeding 40 Gy
- •Recovered from prior surgery
- •No other concurrent investigational agents
- •No concurrent cimetidine
- •No concurrent sorivudine or brivudine
排除标准
- 未提供