An Open-Labeled, Non-Randomized Phase I Study of Alvocidib (Flavopiridol) Administered With Irinotecan (CPT-11) and Cisplatin in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- MTD alvocidib when administered in conjunction with irinotecan hydrochloride and cisplatin
研究概览
简要总结
Phase I trial to study the effectiveness of combining alvocidib, irinotecan hydrochloride, and cisplatin in treating patients who have advanced solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.
详细描述
OBJECTIVES:
I. Determine the maximum tolerated dose of flavopiridol (alvocidib), irinotecan (irinotecan hydrochloride), and cisplatin in patients with advanced solid tumors.
II. Determine the clinical pharmacokinetics of this regimen in these patients. III. Determine, preliminarily, the therapeutic activity of this regimen in these patients.
OUTLINE: This is a dose-escalation study.
Patients are stratified according to the number of prior treatment regimens (0 or 1 vs more than 1). Patients receive irinotecan hydrochloride intravenously (IV) over 30 minutes followed immediately by cisplatin IV over 30 minutes followed 7 hours later by alvocidib IV over 1-4.5 hours weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable 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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed locally advanced or metastatic solid tumor that is refractory to standard therapy or for which no standard therapy exists
- •Evaluable disease
- •No previously untreated CNS metastasis
- •No primary CNS tumors
- •Performance status - Karnofsky 60-100%
- •Performance status - ECOG 0-2
- •Not specified
- •WBC at least 3,000/mm^3
- •Neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Bilirubin no greater than 2.0 mg/dL
- •AST and ALT no greater than 3 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
- •Creatinine no greater than 1.5 mg/dL
- •Creatinine clearance at least 60 mL/min
- •No cardiac arrhythmia
- •No congestive heart failure
- •No myocardial infarction within the past 6 months
- •HIV negative
- •No neuropathy grade 2 or greater
- •No serious or uncontrolled infection
- •No other medical condition or reason that would preclude study participation
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for at least 2 months after study participation
- •At least 4 weeks since prior immunotherapy
- •At least 1 week since prior irinotecan and cisplatin alone
- •At least 4 weeks since other prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- •Not specified
- •At least 4 weeks since prior radiotherapy
- •Not specified
- •Recovered from all prior therapy
- •No concurrent vitamins, antioxidants, or herbal supplements except a daily multivitamin
- •No other concurrent investigational drugs
排除标准
- 未提供
研究组 & 干预措施
Treatment (chemotherapy)
Patients are stratified according to the number of prior treatment regimens (0 or 1 vs more than 1). Patients receive irinotecan hydrochloride IV over 30 minutes followed immediately by cisplatin IV over 30 minutes followed 7 hours later by alvocidib IV over 1-4.5 hours weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: alvocidib (Drug)
Treatment (chemotherapy)
Patients are stratified according to the number of prior treatment regimens (0 or 1 vs more than 1). Patients receive irinotecan hydrochloride IV over 30 minutes followed immediately by cisplatin IV over 30 minutes followed 7 hours later by alvocidib IV over 1-4.5 hours weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: irinotecan hydrochloride (Drug)
Treatment (chemotherapy)
Patients are stratified according to the number of prior treatment regimens (0 or 1 vs more than 1). Patients receive irinotecan hydrochloride IV over 30 minutes followed immediately by cisplatin IV over 30 minutes followed 7 hours later by alvocidib IV over 1-4.5 hours weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: cisplatin (Drug)
结局指标
主要结局
MTD alvocidib when administered in conjunction with irinotecan hydrochloride and cisplatin
时间窗: Course 1
Defined as the dose one level below the dose at which two or more of the patients in the initial cohort experience dose limiting toxicity (DLT) during the first treatment course. DLT is defined as the occurrence of Grade 4 hematologic toxicity, Grade 3 or 4 non-hematologic toxicity including diarrhea despite antidiarrheal prophylaxis, or any delay in treatment resulting in less than 2 treatments in 3 weeks.
次要结局
- Clinical pharmacokinetics of the regimen(Week 1 of courses 1 and 2)
- Therapeutic activity of alvocidib in combination with irinotecan hydrochloride in patients with advanced solid tumors(After 2 courses of treatment)
- Safety and tolerability(Weekly)