Pharmacokinetic Boosting of Osimertinib

• Status: Recruiting
• Trial end date: 2021-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Academisch Ziekenhuis Maastricht
• Collaborators: The Netherlands Cancer Institute; ZonMw: The Netherlands Organisation for Health Research and Development
• Treatments: Cobicistat; Osimertinib

Criteria

Inclusion Criteria:

• 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.