Pilot Pharmacokinetic Study of Dose Adjustment of Vinorelbine in Patients With Varying Degree of Liver Dysfunction
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 47
- 试验地点
- 2
- 主要终点
- Number of Participants With Grade 3 and 4 Toxicities
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as vinorelbine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This pilot trial is studying the side effects and best dose of vinorelbine in treating patients with advanced solid tumors that have not responded to treatment and liver dysfunction.
详细描述
OBJECTIVES:
- To correlate indocyanine green and lidocaine metabolism with vinorelbine ditartrate pharmacokinetics in patients with advanced, refractory solid tumors and varying degrees of liver dysfunction.
- To determine the pharmacokinetics of vinorelbine ditartrate in these patients.
- To test a plan of dose adjustment for vinorelbine ditartrate administration in these patients.
OUTLINE: Patients are stratified according to extent of clinical liver dysfunction (normal vs mild vs moderate vs severe).
Patients receive dose-adjusted vinorelbine ditartrate IV over 10 minutes once weekly in the absence of disease progression or unacceptable toxicity. Patients achieving an objective complete response receive 2 additional courses of study therapy.
Patients undergo blood sample collection periodically during study for pharmacokinetic and pharmacodynamic correlative studies. Blood is also collected after patients receive lidocaine IV push and indocyanine green (ICG) IV push. Samples are analyzed for whole blood and plasma concentrations of vinorelbine ditartrate and its metabolites by high performance liquid chromatography (15) or by liquid chromatography/tandem mass spectrometry assay. Samples are also analyzed for ICG clearance and lidocaine hydrochloride metabolic capacity by fluorescent polarization immunoassay.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Moderate Liver Dysfunction
干预措施: pharmacological study (Other)
Mild Liver Dysfunction
干预措施: indocyanine green (Drug)
Moderate Liver Dysfunction
干预措施: indocyanine green (Drug)
Normal Liver Function
干预措施: mass spectrometry (Other)
Normal Liver Function
干预措施: pharmacological study (Other)
Normal Liver Function
干预措施: indocyanine green (Drug)
Normal Liver Function
干预措施: lidocaine (Drug)
Normal Liver Function
干预措施: vinorelbine ditartrate (Drug)
Normal Liver Function
干预措施: high performance liquid chromatography (Other)
Normal Liver Function
干预措施: intracellular fluorescence polarization analysis (Other)
Normal Liver Function
干预措施: liquid chromatography (Other)
Mild Liver Dysfunction
干预措施: lidocaine (Drug)
Mild Liver Dysfunction
干预措施: vinorelbine ditartrate (Drug)
Mild Liver Dysfunction
干预措施: high performance liquid chromatography (Other)
Mild Liver Dysfunction
干预措施: intracellular fluorescence polarization analysis (Other)
Mild Liver Dysfunction
干预措施: liquid chromatography (Other)
Mild Liver Dysfunction
干预措施: mass spectrometry (Other)
Mild Liver Dysfunction
干预措施: pharmacological study (Other)
Moderate Liver Dysfunction
干预措施: lidocaine (Drug)
Moderate Liver Dysfunction
干预措施: vinorelbine ditartrate (Drug)
Moderate Liver Dysfunction
干预措施: high performance liquid chromatography (Other)
Moderate Liver Dysfunction
干预措施: intracellular fluorescence polarization analysis (Other)
Moderate Liver Dysfunction
干预措施: liquid chromatography (Other)
Moderate Liver Dysfunction
干预措施: mass spectrometry (Other)
Severe Liver Dysfunction
干预措施: indocyanine green (Drug)
Severe Liver Dysfunction
干预措施: lidocaine (Drug)
Severe Liver Dysfunction
干预措施: vinorelbine ditartrate (Drug)
Severe Liver Dysfunction
干预措施: high performance liquid chromatography (Other)
Severe Liver Dysfunction
干预措施: intracellular fluorescence polarization analysis (Other)
Severe Liver Dysfunction
干预措施: liquid chromatography (Other)
Severe Liver Dysfunction
干预措施: mass spectrometry (Other)
Severe Liver Dysfunction
干预措施: pharmacological study (Other)
结局指标
主要结局
Number of Participants With Grade 3 and 4 Toxicities
时间窗: 3 weeks after the stop of treatment
Grade 3 \& 4 toxicities at least possible related to study drugs during any cycle of treatment. Toxicity graded according to Common Terminology Criteria for Adverse Events version 2.0.
Area Under the Curve
时间窗: 2 months post treatment
Pharmacokinetics were evaluated in patients with sufficient dosing information and plasma concentration versus time data over 0-24 hours following vinorelbine infusion to allow calculation of area-under-the-curve from zero to 24 hours after infusion (AUC0-24). Furthermore, dose-normalization of AUC0-24 to the standard 30 mg/m2 dose was performed to allow evaluation of the relationship between liver function and AUC of vinorelbine. Data were collected at 0 and 24 hours post-dose.
次要结局
未报告次要终点