A Phase I Trial of ZD1839 With Capecitabine in Patients With Advanced Solid Tumors (Formerly a Phase I Trial of ZD1839 With Capecitabine and Celecoxib)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Maximum-tolerated dose (MTD) defined as the those below that results in dose-limiting toxicity (DLT) in >= 2 of 6 new patients, as assessed by CTCAE version 3.0
研究概览
简要总结
This phase I trial is studying the side effects and best dose of gefitinib and capecitabine in treating patients with advanced solid tumors. Biological therapies such as gefitinib may interfere with the growth of tumor cells and slow the growth of solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining gefitinib and capecitabine may kill more tumor cells
详细描述
OBJECTIVES:
I. Determine the maximum tolerated dose of gefitinib and capecitabine in patients with advanced solid tumors.
II. Determine the dose-limiting toxic effects of this regimen in these patients.
III. Determine the pharmacologic profile of this regimen in these patients.
OUTLINE: This is a dose-escalation study of gefitinib and capecitabine.
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 advanced solid tumor that is refractory to standard therapy or for which no standard therapy exists
- •No uncontrolled brain metastases, including symptomatic lesions or lesions requiring treatment (e.g., glucocorticoids and/or anticonvulsants)
- •Performance status - ECOG 0-2
- •At least 12 weeks
- •WBC at least 3,000/mm^3
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Hemoglobin at least 9 g/dL
- •Bilirubin no greater than 1.5 mg/dL
- •AST and ALT no greater than 2.5 times upper limit of normal (5 times ULN if liver metastases present)
- •Creatinine no greater than 1.5 mg/dL
- •Creatinine clearance at least 60 mL/min
- •No active infections
- •No other serious concurrent systemic disorders that would preclude study participation
- •No other malignancy
- •No prior hypersensitivity to sulfonamide-based drugs, nonsteroidal anti-inflammatory drugs, or fluorouracil
- •No documented dihydropyrimidine dehydrogenase deficiency
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No concurrent immunotherapy
- •At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- •No concurrent hormonal therapy
- •At least 28 days since prior radiotherapy
- •No concurrent radiotherapy
- •At least 4 weeks since prior investigational agents
- •No other concurrent experimental medications
- •No concurrent drugs known to induce cytochrome P450 3A4 (e.g., rifampin, phenytoin, carbamazepine, or barbiturates)
排除标准
- 未提供
研究组 & 干预措施
Treatment (capecitabine, gefitinib)
Patients receive oral gefitinib once daily on days 1-14 and oral capecitabine twice daily on days 8-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gefitinib and capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.
干预措施: capecitabine (Drug)
Treatment (capecitabine, gefitinib)
Patients receive oral gefitinib once daily on days 1-14 and oral capecitabine twice daily on days 8-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gefitinib and capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.
干预措施: gefitinib (Drug)
Treatment (capecitabine, gefitinib)
Patients receive oral gefitinib once daily on days 1-14 and oral capecitabine twice daily on days 8-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gefitinib and capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.
干预措施: pharmacological study (Other)
Treatment (capecitabine, gefitinib)
Patients receive oral gefitinib once daily on days 1-14 and oral capecitabine twice daily on days 8-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gefitinib and capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Maximum-tolerated dose (MTD) defined as the those below that results in dose-limiting toxicity (DLT) in >= 2 of 6 new patients, as assessed by CTCAE version 3.0
时间窗: 28 days
DTL defined as any grade 3 or greater non-hematological toxicity, and grade 3 or greater skin rash, grade 4 thrombocytopenia and/or neutropenia as assessed by CTCAE version 3.0
时间窗: 28 days
Pharmacological profile
时间窗: At baseline, at 30 minutes, at 1, 2, 3, and 4 hours of days 8, 14, and 21 (course 1)
次要结局
未报告次要终点