Pharmacokinetic Boosting of Osimertinib (POP-NSCLC)
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|ClinicalTrials.gov Identifier: NCT03858491|
Recruitment Status : Not yet recruiting
First Posted : February 28, 2019
Last Update Posted : March 1, 2019
|Condition or disease||Intervention/treatment||Phase|
|Non Small Cell Lung Cancer||Drug: Cobicistat||Early Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||In this study a group of patients will receive cobicistat as add-on on their regular treatment with osimertinib. All patients experience low osimertinib trough concentration levels when treated with the regular osimertinib dose (80 mg per day).|
|Masking:||None (Open Label)|
|Official Title:||Pharmacokinetic Boosting of Osimertinib in Patients With Non-small Cell Lung Cancer.|
|Estimated Study Start Date :||March 1, 2019|
|Estimated Primary Completion Date :||October 31, 2019|
|Estimated Study Completion Date :||December 31, 2019|
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).
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).
Other Name: Tybost
- Osimertinib AUC [ Time Frame: 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.
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0. [ Time Frame: Three weeks ]
The safety of the combination therapy will be evaluated and scored using NCI CTCAE v4.0. The investigators will evaluate the number of patients that experience treatment-related adverse events. Additionally, the investigators will describe the adverse events which are most common in the lung cancer patients.
Participants will be asked to keep up a patient diary with problems they have experienced during the study.
- Cmax of osimertinib [ Time Frame: Three weeks ]The maximum plasma of osimertinib will be determined
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03858491
|Contact: Ard van Veelen, MScemail@example.com|
|Contact: Sander Croes, MSc, PhDfirstname.lastname@example.org|
|Study Director:||Sander Croes, MSc, PhD||Maastricht University Medical Centre+ (MUMC+)|