Ignite Creation Date:
2025-12-25 @ 1:26 AM
Ignite Modification Date:
2025-12-27 @ 11:06 PM
Study NCT ID:
NCT05748093
Status:
RECRUITING
Last Update Posted:
2024-08-09
First Post:
2023-02-02
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Improving Osimertinib Exposure and Cost-effectiveness Using Pharmacokinetic Boosting With Cobicistat
Sponsor:
Maastricht University Medical Center
Organization:
Study Overview
Official Title:
Improving Osimertinib Exposure and Cost-effectiveness Using Pharmacokinetic Boosting With Cobicistat (OSIBOOST 2)
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
OSIBOOST 2
Brief 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.
* 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.
Detailed Description:
In 2016 Osimertinib was registered for the treatment of patients with metastatic Non-Small Cell Lung Cancer (NSCLC) with an activating Epidermal Growth Factor Receptor (EGFR) mutation, initially only for patients with the T790M resistance mutation, but since 2018 also in the first line treatment. Use of osimertinib in the first line provides improved overall survival and progression-free survival, more potent efficacy against brain metastases, and better tolerability compared to older generation EGFR tyrosine kinase inhibitors (EGFR-TKIs). The downside of osimertinib is that -like many new anticancer agents- it is highly expensive (over €70 000 per patient per year in the Netherlands). In a period of five years, healthcare costs associated with expensive medication have risen from €1.71 billion to €2.46 billion per year in the Netherlands. The Dutch Cancer Society has warned that this astronomical cost increase will start to suffocate the national health care budget. In order to safeguard sustained affordability and accessibility of oncological healthcare, improving cost-effectiveness of available drugs is of paramount importance. In a previous study, we have demonstrated that osimertinib exposure may be boosted, through concomitant use of cobicistat, as a result of CYP3A4 inhibition. We now aim to apply pharmacokinetic (PK) boosting in order to improve osimertinib exposure and cost-effectiveness, without impacting treatment efficacy and safety.
This trial is designed to study whether pharmacokinetic boosting may alleviate these issues. In the first cohort, we will assess whether PK-boosting is able to reduce the amount of osimertinib which a patient needs to take. In order to assess this, the patient will receive cobicistat (the booster drug) and we will measure the amount of osimertinib and its metabolite in blood. Afterwards, the researchers and physicians may calculate how much osimertinib a patient actually needs. Ideally this will both reduce the amount of osimertinib that a patient needs to take, as well as reduce the price-tag of the overall treatment. In the second cohort, we will assess whether PK-boosting is a viable alternative to dose-doubling osimertinib. Some patients with NSCLC develop progressive CNS metastases despite osimertinib therapy. There is an indication that increasing the osimertinib dosage to double the standard therapy might provide longer/better treatment efficacy in these patients. Because of the tremendous cost associated with double-dosing osimertinib, most health care insurance providers in the Netherlands do not cover this therapy. In cohort 2 we look to find out whether PK-boosting might provide a similar effect to increasing the dosage, for a far more affordable price-tag.
This trial is designed to study whether pharmacokinetic boosting may alleviate these issues. In the first cohort, we will assess whether PK-boosting is able to reduce the amount of osimertinib which a patient needs to take. In order to assess this, the patient will receive cobicistat (the booster drug) and we will measure the amount of osimertinib and its metabolite in blood. Afterwards, the researchers and physicians may calculate how much osimertinib a patient actually needs. Ideally this will both reduce the amount of osimertinib that a patient needs to take, as well as reduce the price-tag of the overall treatment. In the second cohort, we will assess whether PK-boosting is a viable alternative to dose-doubling osimertinib. Some patients with NSCLC develop progressive CNS metastases despite osimertinib therapy. There is an indication that increasing the osimertinib dosage to double the standard therapy might provide longer/better treatment efficacy in these patients. Because of the tremendous cost associated with double-dosing osimertinib, most health care insurance providers in the Netherlands do not cover this therapy. In cohort 2 we look to find out whether PK-boosting might provide a similar effect to increasing the dosage, for a far more affordable price-tag.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 2023-505700-35-00 | CTIS | None | View |