Improving Osimertinib Exposure and Cost-effectiveness Using Pharmacokinetic Boosting With Cobicistat
Recruiting · NCT05748093 · Interventional (participants receive a specific treatment) · Lead sponsor: Maastricht University Medical Center
View the official record on ClinicalTrials.gov →Interventions studied
What this trial is about
The goal of this clinical trial is to assess the feasibility of pharmacokinetically boosting osimertinib using cobicistat in order to improve osimertinib exposure in individual patients with advanced NSCLC (Non-Small Cell Lung Cancer) with mutated EGFR (Epidermal Growth Factor Receptor). The main questions it aims to answer are: * Cohort 1: Does concurrent use of osimertinib and cobicistat allow for osimertinib weekly intake reductions? If so, how much can the intake be reduced while retaining clinically effective exposure? * Cohort 2: Does concurrent use of osimertinib and cobicistat allow for improved penetration of osimertinib in the central nervous system, in patients with CNS (central nervous system) oligoprogression? Participants who are taking osimertinib in regular care will receive cobicistat in addition to their other medication. They will undergo blood sampling to measure the amount of osimertinib in blood, and measure the effect of boosting. Additionally, in cohort 1 patients will be dose-reduced if their exposure levels allow.
Who can take part
Inclusion criteria
- In order to be eligible to participate in this cohort 1, a subject must meet all of the following criteria:
- The patient is set to receive osimertinib 80 mg QD as part of their standard treatment plan
- The patient has a World Health Organization (WHO) Performance Status (PS) of ≤2.
- The patient is 18 years or older
- The patient is able and willing to sign informed consent
- The patient is able and willing to undergo blood sampling
- The patient has non-squamous advanced EGFR-mutated NSCLC with no signs of imminent progression (CT confirmed). If the patient does have signs of progression, they are only eligible if their treating physician deems the treatment to be appropriate beyond progression.
- The patient consents to their blood being analysed for CYP3A-genotype
- In order to be eligible to participate in this cohort 2, a subject must meet all of the following criteria:
- The patient is set to receive osimertinib 80 mg QD as part of their standard treatment plan
- The patient has a World Health Organization (WHO) Performance Status (PS) of ≤2.
- The patient is 18 years or older
- The patient is able and willing to sign informed consent
- The patient is able and willing to undergo blood sampling
- The patient has non-squamous EGFR-mutated NSCLC with radiologically confirmed progressive (RECIST v1.1), but asymptomatic intracranial metastasis, not in an eloquent area (to be discussed with neurologist). Furthermore, the disease is controlled extracranially (no RECIST v1.1 progression).
Exclusion criteria
- A potential participant who meets any of the following criteria will be excluded from participation in this study:
- The patient does not take any other drug which is known to strongly inhibit CYP3A4/CYP3A5 activity
- The patient does not take any other drug which is metabolized by CYP3A4/CYP3A5 and which has a small therapeutic window
- The patient does not take any drug or product which may otherwise affect CYP3A4/CYP3A5 metabolic activity
- The patient does not have impaired gastrointestinal function
- The patient is neither pregnant nor breastfeeding
- The patient does not have any contra-indication for cobicistat prescription, as listed in the summary of product characteristics for cobicistat
Where it is running
1 location listed.
- MaastrichtUMC - Maastricht, Limburg, Netherlands