A Phase I Pharmacokinetic Study of STI571 in Patients With Advanced Malignancies and Varying Levels of Liver Dysfunction
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- MTD defined based on the toxicities observed during the first cycle of treatment
研究概览
简要总结
Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Phase I trial to study the effectiveness of imatinib mesylate in treating patients who have advanced cancer and liver dysfunction
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose and dose-limiting toxicity of imatinib mesylate in patients with advanced malignancies and varying degrees of liver dysfunction.
II. Determine the effects of hepatic dysfunction on the pharmacodynamics and pharmacokinetics of this drug in these patients.
III. Determine the non-dose-limiting toxic effects of this drug in these patients.
IV. Determine the response rate of these patients treated with this drug. V. Correlate the Childs-Pugh classification of hepatic dysfunction with observed toxic effects, pharmacodynamics, and pharmacokinetics of this drug in these patients.
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
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed surgically incurable solid tumor orhematologic malignancy for which no standard or palliative therapy exists oris no longer effective
- •All tumor types are eligible, including:
- •Chronic myelogenous leukemia or other Philadelphia chromosome-positive leukemia OR
- •Gastrointestinal stromal tumors
- •Patients with gliomas that require corticosteroids or anticonvulsants must beon a stable dose and seizure-free for 1 month
- •No unstable or untreated (non-irradiated) brain metastases
- •Performance status - ECOG 0-2
- •Performance status - Karnofsky 60-100%
- •More than 3 months
- •WBC at least 3,000/mm^3
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •No active hemolysis
- •See Surgery
- •No evidence of biliary sepsis
- •Creatinine normal
- •Creatinine clearance at least 60 mL/min
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •Able to swallow pills
- •No other uncontrolled concurrent illness that would preclude study participation
- •No ongoing or active infection
- •No uncontrolled diarrhea
- •No psychiatric illness or social situation that would preclude study compliance
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective barrier contraception during and for 6 months after study completion
- •At least 24 hours since prior colony-stimulating factors
- •No concurrent colony-stimulating factors
- •At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- •See Disease Characteristics
- •See Disease Characteristics
- •At least 4 weeks since prior radiotherapy and recovered
- •See Disease Characteristics
- •At least 10 days since prior placement of shunt for treatment of biliary obstruction
- •At least 14 days since prior major surgery
- •No prior solid organ transplantation
- •No other concurrent investigational agents
- •No concurrent therapeutic doses of warfarin for anticoagulation
- •No other concurrent investigational or commercial agents or therapies for treatment of this disease
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No concurrent acetaminophen of more than 4,000 mg/day
排除标准
- 未提供
研究组 & 干预措施
Treatment (imatinib mesylate)
Patients receive oral imatinib mesylate daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients within each stratum (except normal stratum) receive escalating doses of imatinib mesylate 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
干预措施: imatinib mesylate (Drug)
Treatment (imatinib mesylate)
Patients receive oral imatinib mesylate daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients within each stratum (except normal stratum) receive escalating doses of imatinib mesylate 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
干预措施: pharmacological study (Other)
结局指标
主要结局
MTD defined based on the toxicities observed during the first cycle of treatment
时间窗: 4 weeks
Toxicity evaluation graded according to the NCI common toxicity criteria and relationship to the study drug
时间窗: Up to 4 years
Results will be tabulated by liver dysfunction group.
次要结局
- Pharmacokinetic data(Day 1, 2, 3, 4, 15, 16)
- Responses(Up to 4 years)
- Child-Pugh Classification(Baseline)