Individualized Pemetrexed Dosing in Patients With Non-small Cell Lung Cancer or Mesothelioma Based on Renal Function to Improve Treatment Response
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 5
- 主要终点
- Exposure (AUC) after microdose
研究概览
简要总结
Rationale:
Pemetrexed is a multi-targeted folate antagonist, which is primarily indicated for the treatment of advanced non-small cell lung cancer (NSCLC) and mesothelioma. Dosing of cytotoxic agents like pemetrexed requires balancing the dual risk of sub-therapy and toxicity. Administration of pemetrexed to patients with a creatinine clearance <45 ml/min is currently not advised. Pemetrexed is dosed based on body surface area (BSA), while renal function and dose are the sole determinants for systemic exposure. This causes 3 major issues:
- In patients with renal dysfunction, BSA-based dosing may lead to haematological toxicity
- Patients have to discontinue treatment due to declining renal function, and are withheld effective treatment
- Even in patients with adequate renal function (GFR >45 ml/min) treatment may be improved by individualized dosing based on renal function, resulting in less toxicity. Also, BSA-based dosing may lead to ineffective therapy in patients with above average renal function.
The investigators aim to address these problems.
Objective: The overall main objective is to develop a safe and effective individualized dosing regimen for pemetrexed.
Study design: IMPROVE-III is an explorative microdosing study to assess the extrapolability of microdose-pharmacokinetics to the pharmacokinetics of a therapeutic dose.
Study population: IMPROVE-III includes 10 patients of IMPROVE-I and/or IMPROVE-II.
Intervention: patients will be administered a microdose with subsequent pharmacokinetic assessment.
Main study endpoints: The predictive performance of microdosing to predict full dose pharmacokinetics
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 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
- •≥18 years old
- •Planned for treatment with pemetrexed-based chemotherapy in IMPROVE-I or -II.
- •Eastern Cooperative Oncology Group (ECOG) performance score of 0-2
- •Subject is able and willing to sign the Informed Consent Form
排除标准
- •Conditions that affect haemostasis in a way that blood drawing is complicated (to be assessed by physician)
- •Contraindications for treatment with pemetrexed in line with the summary of product characteristics (SmPC) (except for creatinine clearance <45 ml/min in IMPROVE-I)
- •Hypersensitivity to the active substance or to any of the excipients
- •Pregnancy or lactation
- •Concomitant yellow fever vaccine
- •The presence of clinically relevant pharmacokinetic interactions, according to the current SmPC
研究组 & 干预措施
Microdosing
Patients will be administered a microdose of pemetrexed with subsequent pharmacokinetic assessment. Afterwards the patients will continue in either IMPROVE-I or -II for second pharmacokinetic assessment
干预措施: Pemetrexed (Drug)
结局指标
主要结局
Exposure (AUC) after microdose
时间窗: 1 day
mg\*h/l
The predictive performance of microdosing to predict full dose pharmacokinetics
时间窗: 3 months
Root mean squared relative prediction error (RMSE)
次要结局
未报告次要终点