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Pharmacokinetic Boosting of Osimertinib (OSIBOOST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03858491
Recruitment Status : Recruiting
First Posted : February 28, 2019
Last Update Posted : January 5, 2021
The Netherlands Cancer Institute
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
Ard van Veelen, Academisch Ziekenhuis Maastricht

Brief 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.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Drug: Cobicistat Early Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 26 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: In this study a group of patients will receive cobicistat as add-on on their regular treatment with osimertinib. All patients experience low osimertinib trough concentration levels when treated with the regular osimertinib dose (80 mg per day).
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacokinetic Boosting of Osimertinib in Patients With Non-small Cell Lung Cancer.
Actual Study Start Date : November 1, 2020
Estimated Primary Completion Date : October 31, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

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 Name: Tybost

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. Cmax of osimertinib [ Time Frame: Three weeks ]
    The maximum plasma of osimertinib will be determined

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03858491

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Contact: Ard van Veelen, MSc +31648621180
Contact: Sander Croes, MSc, PhD +31433871431

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Maastricht University Medical Centre Recruiting
Maastricht, Limburg, Netherlands, 6225EC
Contact: Sander Croes   
Antoni van Leeuwenhoek hospital Recruiting
Amsterdam, Noord-Holland, Netherlands, 1066CX
Contact: Egbert Smit         
Sponsors and Collaborators
Academisch Ziekenhuis Maastricht
The Netherlands Cancer Institute
ZonMw: The Netherlands Organisation for Health Research and Development
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Study Director: Sander Croes, MSc, PhD Maastricht University Medical Centre+ (MUMC+)
Publications of Results:
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Responsible Party: Ard van Veelen, Researcher, Academisch Ziekenhuis Maastricht Identifier: NCT03858491    
Other Study ID Numbers: 2018-004290-28
First Posted: February 28, 2019    Key Record Dates
Last Update Posted: January 5, 2021
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Ard van Veelen, Academisch Ziekenhuis Maastricht:
Pharmacokinetic boosting
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action