Pharmacokinetic Boosting of Osimertinib

  • STATUS
    Recruiting
  • End date
    Dec 31, 2021
  • participants needed
    26
  • sponsor
    Academisch Ziekenhuis Maastricht
Updated on 27 January 2021

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.

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.

Details
Condition Non-Small Cell Lung Cancer, nsclc
Treatment Cobicistat
Clinical Study IdentifierNCT03858491
SponsorAcademisch Ziekenhuis Maastricht
Last Modified on27 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: nsclc or Non-Small Cell Lung Cancer?
Do you have any of these conditions: Non-Small Cell Lung Cancer or nsclc?
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 2
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)

Exclusion Criteria

Any concurrent medication that is known to strongly inhibit or induce CYP3A4
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
Clear my responses

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