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Non Small Cell Lung CancerEarly Phase 1OSIBOOSTNCT03858491

Pharmacokinetic Boosting of Osimertinib

A Early Phase 1 study testing Cobicistat in people with Non Small Cell Lung Cancer, run by Academisch Ziekenhuis Maastricht at 2 sites in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non Small Cell Lung Cancer
What is being tested?
Cobicistat
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
2 sitesNetherlands
Study dates
1 Nov 2020to 31 Dec 2021
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).

Who cannot join

  • 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.

Trial locations and contacts

2 sites in 1 country.

Netherlands2 sites

  • Antoni van Leeuwenhoek hospital

    Amsterdam, North Holland, 1066CX

  • Maastricht University Medical Centre

    Maastricht, Limburg, 6225EC

Other trials in Netherlands

About this study

Official title: 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.

Read the 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.

Being tested
Cobicistat
Keywords
Osimertinib, Cobicistat, Pharmacokinetic boosting
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CobicistatDrug

    Also called Tybost

    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).

Study groups in NCT03858491
Study groupRoleWhat they receive
CobicistatExperimentalCobicistat 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).
Receives: Drug: Cobicistat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Osimertinib AUC

    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.

    Measured: Three weeks

Secondary outcomes (2)

  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.

    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.

    Measured: Three weeks

  2. Cmax of osimertinib

    The maximum plasma of osimertinib will be determined

    Measured: Three weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Feb 2019
  2. Study start1 Nov 2020
  3. Primary completion31 Oct 2021
  4. Study completion31 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
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)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03858491
Sponsor's protocol ID
2018-004290-28
Other IDs
2018
Acronym
OSIBOOST
Status last verified
Sep 2022
First submitted
26 Feb 2019
Last updated
26 Sep 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. doi: 10.1056/NEJMoa1713137. Epub 2017 Nov 18.

    PubMed 29151359

  • Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. doi: 10.1056/NEJMoa1612674. Epub 2016 Dec 6.

    PubMed 27959700

  • Lubberman FJE, van Erp NP, Ter Heine R, van Herpen CML. Boosting axitinib exposure with a CYP3A4 inhibitor, making axitinib treatment personal. Acta Oncol. 2017 Sep;56(9):1238-1240. doi: 10.1080/0284186X.2017.1311024. Epub 2017 Apr 7. No abstract available.

    PubMed 28388255

  • Westra N, Kruithof PD, Croes S, van Geel RMJM, Hendriks LEL, Touw DJ, Oude Munnink TH, Mian P. Systematic Evaluation of Osimertinib Population Pharmacokinetic Models in a Cohort of Dutch Adults with Non-Small Cell Lung Cancer. Eur J Drug Metab Pharmacokinet. 2024 Jul;49(4):517-526. doi: 10.1007/s13318-024-00904-5. Epub 2024 Jun 15.

    PubMed 38878145

  • van Veelen A, Gulikers J, Hendriks LEL, Dursun S, Ippel J, Smit EF, Dingemans AC, van Geel R, Croes S. Pharmacokinetic boosting of osimertinib with cobicistat in patients with non-small cell lung cancer: The OSIBOOST trial. Lung Cancer. 2022 Sep;171:97-102. doi: 10.1016/j.lungcan.2022.07.012. Epub 2022 Jul 25.

    PubMed 35933915

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Cobicistat in people with Non Small Cell Lung Cancer, run by Academisch Ziekenhuis Maastricht at 2 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Osimertinib AUC (time frame: Three weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03858491, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2022.

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