The Pharmacokinetic and Safety Profile of UCN-01 in Combination With Irinotecan in Solid Tumors (Primarily Lung, Ovarian and GI Cancers)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
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 with irinotecan in treating patients who have advanced solid tumors.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose and recommended phase II dose of UCN-01 and irinotecan in patients with advanced solid tumors, primarily lung, ovarian, and gastrointestinal tumors.
- Determine the acute and chronic toxicity profile of this regimen in these patients.
- Determine the pharmacokinetics of this regimen in these patients.
- Determine, preliminarily, the anti-tumor effect of this regimen in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive UCN-01 IV over 3 hours on day 1 and irinotecan IV over 90 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of UCN-01 and irinotecan 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. At least 6 patients are treated at the recommended phase II dose.
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 malignancy that is metastatic or unresectable and for which standard curative or palliative therapy does not exist or is no longer effective
- •Gastrointestinal, lung, and ovarian malignancies are given priority
- •No brain metastases
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status
- •ECOG 0-2 OR
- •Karnofsky 60-100%
- •Life expectancy
- •More than 3 months
- •Hematopoietic
- •WBC at least 3,000/mm^3
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Bilirubin normal
- •AST/ALT no greater than 2.5 times upper limit of normal (ULN)
- •Creatinine normal OR
- •Creatinine clearance at least 60 mL/min
- •Cardiovascular
- •No symptomatic coronary artery disease
- •No symptomatic cardiac dysfunction
- •No symptoms suggestive of coronary artery disease
- •LVEF at least 50%
- •No symptomatic pulmonary dysfunction
- •FEV_1 greater than 75% of predicted
- •DLCO greater than 75% of predicted
- •Amylase no greater than 2 times ULN
- •No other concurrent uncontrolled illness
- •No ongoing or active infection
- •No psychiatric illness or social situation that would preclude study compliance
- •No diabetes mellitus or random glucose more than 200 mg/dL
- •No prior allergic reaction attributed to compounds of similar biological or chemical composition to UCN-01 or irinotecan (including rash and systemic allergic reaction causing hypotension and respiratory distress)
- •No chronic diarrhea (more than 5 stools/day)
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception for 14 days before, during, and for at least 30 days after study participation
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •Not specified
- •Chemotherapy
- •At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- •Prior UCN-01 and irinotecan allowed
- •Endocrine therapy
- •Not specified
- •Radiotherapy
- •At least 4 weeks since prior radiotherapy and recovered
- •No prior mediastinal radiation
- •Not specified
- •At least 14 days since prior warfarin
- 另有 3 项未显示
排除标准
- 未提供