Phase I Study of Flavopiridol in Combination With 5-Fluorouracil, Leucovorin and Irinotecan in Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Number and severity of toxicity incidents of alvocidib, 5-fluorouracil, leucovorin calcium with and without irinotecan hydrochloride, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
研究概览
简要总结
Phase I trial to study the effectiveness of combining flavopiridol, fluorouracil, and leucovorin with or without irinotecan in treating patients who have advanced cancer. 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, fluorouracil, and leucovorin calcium with or without irinotecan in patients with advanced malignancy.
II. Assess the toxic effects of these regimens in these patients. III. Determine the clinical response in patients treated with these regimens.
OUTLINE: This a dose-escalation study of flavopiridol (FLAVO), fluorouracil (5-FU), and irinotecan. Patients are assigned to 1 of 2 groups. Groups I and II are conducted sequentially.
Group I: Patients receive FLAVO IV over 24 hours on day 1 and leucovorin calcium (CF) IV and 5-FU IV over 1.5 hours daily on days 2-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of FLAVO and 5-FU until the maximum tolerated doses (MTD) are determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting 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 malignancy
- •Unresectable tumor
- •No known standard therapy with curative potential or capability of extending life expectancy
- •No untreated CNS metastases
- •Performance status - ECOG 0-2
- •At least 12 weeks
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Hemoglobin at least 8 g/dL
- •Direct bilirubin no greater than upper limit of normal (ULN)
- •AST no greater than 3 times ULN (5 times ULN if liver metastases present)
- •Creatinine no greater than 1.5 times ULN
- •No New York Heart Association class III or IV heart disease
- •No seizure disorder
- •No uncontrolled infection
- •No baseline diarrhea, defined as at least 4 loose or liquid stools/day
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •More than 4 weeks since prior biologic therapy
- •More than 4 weeks since prior immunotherapy
- •No concurrent immunotherapy
- •More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and fully recovered from acute reversible effects
- •No other concurrent chemotherapy
- •More than 4 weeks since prior radiotherapy
- •No prior radiotherapy to more than 25% of bone marrow
- •No concurrent radiotherapy
- •No other concurrent ancillary investigational therapy
排除标准
- 未提供
研究组 & 干预措施
Treatment (alvocidib, combination chemotherapy)
Group I: Patients receive FLAVO IV over 24 hours on day 1 and CF IV and 5-FU IV over 1.5 hours daily on days 2-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of FLAVO and 5-FU until the MTD are determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.
Once the MTDs for FLAVO and 5-FU are determined, patients receive FLAVO, CF, and 5-FU as in group I plus irinotecan IV over 1.5 hours on day 1. Courses repeat as in group I. Cohorts of 3-6 patients receive escalating doses of irinotecan until the MTD is determined. The MTD is defined as in group I.
干预措施: alvocidib (Drug)
Treatment (alvocidib, combination chemotherapy)
Group I: Patients receive FLAVO IV over 24 hours on day 1 and CF IV and 5-FU IV over 1.5 hours daily on days 2-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of FLAVO and 5-FU until the MTD are determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.
Once the MTDs for FLAVO and 5-FU are determined, patients receive FLAVO, CF, and 5-FU as in group I plus irinotecan IV over 1.5 hours on day 1. Courses repeat as in group I. Cohorts of 3-6 patients receive escalating doses of irinotecan until the MTD is determined. The MTD is defined as in group I.
干预措施: leucovorin calcium (Drug)
Treatment (alvocidib, combination chemotherapy)
Group I: Patients receive FLAVO IV over 24 hours on day 1 and CF IV and 5-FU IV over 1.5 hours daily on days 2-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of FLAVO and 5-FU until the MTD are determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.
Once the MTDs for FLAVO and 5-FU are determined, patients receive FLAVO, CF, and 5-FU as in group I plus irinotecan IV over 1.5 hours on day 1. Courses repeat as in group I. Cohorts of 3-6 patients receive escalating doses of irinotecan until the MTD is determined. The MTD is defined as in group I.
干预措施: fluorouracil (Drug)
Treatment (alvocidib, combination chemotherapy)
Group I: Patients receive FLAVO IV over 24 hours on day 1 and CF IV and 5-FU IV over 1.5 hours daily on days 2-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of FLAVO and 5-FU until the MTD are determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.
Once the MTDs for FLAVO and 5-FU are determined, patients receive FLAVO, CF, and 5-FU as in group I plus irinotecan IV over 1.5 hours on day 1. Courses repeat as in group I. Cohorts of 3-6 patients receive escalating doses of irinotecan until the MTD is determined. The MTD is defined as in group I.
干预措施: irinotecan hydrochloride (Drug)
结局指标
主要结局
Number and severity of toxicity incidents of alvocidib, 5-fluorouracil, leucovorin calcium with and without irinotecan hydrochloride, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
时间窗: Up to 5 years
次要结局
- Number of responses (complete response, partial response, stable disease, and progressive disease) assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)(Up to 5 years)