Improving Osimertinib Exposure and Cost-effectiveness Using Pharmacokinetic Boosting With Cobicistat (OSIBOOST 2)

Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 4
SUMMARY

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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

⁃ 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).

Locations
Other Locations
Netherlands
MaastrichtUMC
RECRUITING
Maastricht
Contact Information
Primary
Paul Kruithof, PharmD, MSc
paul.kruithof@mumc.nl
+31433871881
Backup
Sander Croes, PharmD, PhD
s.croes@mumc.nl
+31433871881
Time Frame
Start Date: 2024-04-01
Estimated Completion Date: 2026-09-01
Participants
Target number of participants: 60
Treatments
Experimental: Cohort 1: Adjusting osimertinib treatment plans with concomitant pk-boosting
Feasibility of using pharmacokinetic boosting and TDM to individualize treatment plans and dosage for osimertinib, in patients with advanced NSCLC with mutated EGFR. In this cohort, patients will receive cobicistat for pharmacokinetic boosting of standard osimertinib treatment. Afterwards, they will receive personalised treatment plans, guided by therapeutic drug monitoring.
Experimental: Cohort 2: Improving osimertinib CNS penetration in patients with neurometastases
Assessing whether pharmacokinetic boosting can improve CNS penetration of osimertinib, in patients with advanced NSCLC with mutated EGFR with asymptomatic CNS oligoprogression. Patients who experience progressive disease intracranially, are sometimes dose-escalated to try and improve osimertinib intracranial exposure. This study will look to demonstrate the feasibility of using a PK-booster instead, potentially providing patients the benefits of higher intracranial treatment efficacy, without needing to take extra osimertinib.
Sponsors
Leads: Maastricht University Medical Center

This content was sourced from clinicaltrials.gov