NCT03858491

Pharmacokinetic Boosting of Osimertinib

Pharmacokinetic Boosting of Osimertinib in Patients With Non-small Cell Lung Cancer.

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 11 (actual)
• Sponsor: Academisch Ziekenhuis Maastricht · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Non Small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	Cobicistat	Cobicistat will be added to the treatment with osimertinib. The initial dose will be 150 mg cobicistat, which equals the dose used in the treatment of HIV-infected patients. If this dose is well tolerated and the increase in exposure of osimertinib is not sufficient, the dose of cobicistat will gradually be escalated to 600 mg per day (150 mg cobicistat, four times per day).

Timeline

• Start date: 2020-11-01
• Primary completion: 2021-10-31
• Completion: 2021-12-31
• First posted: 2019-02-28
• Last updated: 2022-09-26

Locations

2 sites across 1 country: Netherlands