Pharmacokinetic Boosting of Osimertinib (OSIBOOST)

September 23, 2022 updated by: Ard van Veelen, Academisch Ziekenhuis Maastricht

Pharmacokinetic Boosting of Osimertinib in Patients With Non-small Cell Lung Cancer.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Limburg
      • Maastricht, Limburg, Netherlands, 6225EC
        • Maastricht University Medical Centre
    • Noord-Holland
      • Amsterdam, Noord-Holland, Netherlands, 1066CX
        • Antoni van Leeuwenhoek Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cobicistat
Cobicistat will serve as experimental drugs, and will be added to the regular treatment with osimertinib. Combination-treatment will be started at 150 milligram cobicistat, and can be increased to a maximum daily dose of 600 milligram cobicistat (four times 150 milligram).
Drug: Cobicistat
Cobicistat will be added to the treatment with osimertinib. The initial dose will be 150 mg cobicistat, which equals the dose used in the treatment of HIV-infected patients. If this dose is well tolerated and the increase in exposure of osimertinib is not sufficient, the dose of cobicistat will gradually be escalated to 600 mg per day (150 mg cobicistat, four times per day).
Other Names:
  • Tybost

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Osimertinib AUC
Time Frame: Three weeks
Exposure to osimertinib will be measured at the start of the study and after three weeks of treatment with cobicistat. This will be done by measuring the concentration of osimertinib four times during the day (pre-dose and two, four and eight hour post-dose), which will be used to calculate the AUC of osimertinib.
Three weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
Time Frame: Three weeks

The safety of the combination therapy will be evaluated and scored using NCI CTCAE v4.0. The investigators will evaluate the number of patients that experience treatment-related adverse events. Additionally, the investigators will describe the adverse events which are most common in the lung cancer patients.

Participants will be asked to keep up a patient diary with problems they have experienced during the study.
Three weeks
Cmax of osimertinib
Time Frame: Three weeks
The maximum plasma of osimertinib will be determined
Three weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Academisch Ziekenhuis Maastricht

Collaborators

The Netherlands Cancer Institute
ZonMw: The Netherlands Organisation for Health Research and Development

Investigators

  • Study Director: Sander Croes, MSc, PhD, Maastricht University Medical Centre+ (MUMC+)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2020

Primary Completion (Actual)

October 31, 2021

Study Completion (Actual)

December 31, 2021

Study Registration Dates

First Submitted

February 26, 2019

First Submitted That Met QC Criteria

February 27, 2019

First Posted (Actual)

February 28, 2019

Study Record Updates

Last Update Posted (Actual)

September 26, 2022

Last Update Submitted That Met QC Criteria

September 23, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2018-004290-28

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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