Pharmacokinetic Boosting of Osimertinib in Patients With Non-small Cell Lung Cancer.
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 2
- 主要终点
- Osimertinib AUC
研究概览
简要总结
The main objective of this study is to evaluate if systemic exposure of osimertinib (i.e. AUC) is increased when osimertinib is co-administered with cobicistat in patients with relatively low plasma trough concentration while receiving the standard osimertinib dose.
详细描述
Osimertinib is a new targeted agent registered for the treatment of patients with EGFR-mutated NSCLC. However, the costs of those new treatments are extremely high. Osimertinib is mainly metabolized by CYP3A4, and partially by CYP3A5. Combination of osimertinib with a strong CYP3A4-inhibitor may result in a smaller first-pass effect and a decreased clearance of osimertinib, thereby increasing the exposure to osimertinib.
Cobicistat is a strong CYP3A4-inhibitor, this mechanism may be used to boost osimertinib, as is done for other drugs, mainly drugs used to treat HIV-infected patients.
Using this personalized treatment approach and combining the concepts of therapeutic drug monitoring (TDM) and pharmacokinetic boosting, osimertinib therapy could become much more cost-effective. By reducing the necessary dose of osimertinib, this strategy may ultimately result in a significant reduction in drug costs, as the additional expenditure for the CYP3A4 inhibitor and blood sample analysis are negligible compared to the price of osimertinib.
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
- •Patients with EGFR-mutated NSCLC receiving standard treatment with osimertinib for at least 2 months (steady state), without any signs of disease progression, or during treatment beyond progression, if treatment continuation is expected for multiple months. After anticipated EMA approval of osimertinib adjuvant therapy, patients on adjuvant osimertinib treatment may also participate on the following conditions; If they are receiving standard treatment with osimertinib for at least 2 months (steady state), and if treatment will be continued for a longer period than necessary for participation in the OSIBOOST trial.
- •Age ≥ 18 years
- •WHO performance status ≤
- •Able and willing to give written informed consent.
- •Able and willing to undergo blood sampling for pharmacokinetic analysis.
- •Patients with osimertinib plasma trough concentration below 195 ng/mL. Plasma trough concentration of osimertinib will be determined in another study (METC MUMC: 2018-0800).
排除标准
- •Any concurrent medication that is known to strongly inhibit or induce CYP3A
- •Any concurrent medication that is primarily metabolized by CYP3A4 with a narrow therapeutic window.
- •Impairment of gastrointestinal function that may alter the absorption of osimertinib or cobicistat (e.g. ulcerative disease, uncontrolled nausea or vomiting, malabsorption syndrome, small bowel resection).
- •Refusing to refrain from consuming CYP3A4 influencing products, e.g. grapefruit(juice), St. John's wort.
- •Pregnancy or breast feeding
- •Child-Pugh score class C, chronic liver disease.
研究组 & 干预措施
Cobicistat
Cobicistat will serve as experimental drugs, and will be added to the regular treatment with osimertinib. Combination-treatment will be started at 150 milligram cobicistat, and can be increased to a maximum daily dose of 600 milligram cobicistat (four times 150 milligram).
干预措施: Cobicistat (Drug)
结局指标
主要结局
Osimertinib AUC
时间窗: Three weeks
Exposure to osimertinib will be measured at the start of the study and after three weeks of treatment with cobicistat. This will be done by measuring the concentration of osimertinib four times during the day (pre-dose and two, four and eight hour post-dose), which will be used to calculate the AUC of osimertinib.
次要结局
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.(Three weeks)
- Cmax of osimertinib(Three weeks)
研究者
Ard van Veelen
Researcher
Academisch Ziekenhuis Maastricht