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Non-Small Cell Lung CancerPhase 2OSIBBBOOSTNCT07485452

Boosting Osimertinib Blood Brain Barrier Penetration

A Phase 2 study testing Osimertinib & febuxostat in people with Non-Small Cell Lung Cancer, run by Maastricht University Medical Center at 2 sites in Netherlands.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The goal of this proof-of-concept clinical study is to determine the effect of combining osimertinib with febuxostat on cerebrospinal fluid concentrations of osimertinib in patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC). 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?
Osimertinib & febuxostat
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
2 sitesNetherlands
Study dates
Jun 2026to Jun 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • In order to be eligible to participate in this study, a subject must meet all of the following criteria:
  • The patient has metastatic EGFR-mutated NSCLC and is treated with osimertinib as part of regular care with CT-confirmed stable disease or better. Patients with (signs of) disease progression, are also eligible if their treating physician deems the treatment to be appropriate beyond progression and the expected osimertinib treatment duration is at least 1 month.
  • The patient has an European Cooperative Oncology Group (ECOG) performance status (PS) of 0-2.
  • The patient is 18 years of age or older.
  • The patient is able and willing to sign informed consent prior to any tests or procedures.
  • The patient is able and willing to undergo additional blood sampling for e.g. therapeutic drug monitoring.
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  • The patient is able and willing to undergo lumbar punctions to obtain CSF.
  • The patient must meet the criteria stated in the approved regulatory indication(s) for osimertinib where the clinical study will be performed and agree to the restrictions, monitoring, and dose-adjustment criteria stipulated in the associated product label.
  • The patient does not harbour the ABCG2 34G>A single nucleotide polymorphism.
  • The patient does not have any central nervous system (CNS) metastases.
  • Patients with HBV are only eligible for inclusion if they meet all the following criteria:
  • Demonstrated absence of HCV co-infection or history of HCV co-infection
  • Demonstrated absence of HIV infection
  • Participants with active HBV infection are eligible if they are:
  • Receiving anti-viral treatment for at least 6 weeks prior to study treatment, HBV DNA is suppressed to <100 IU/mL and transaminase levels are below ULN.
  • Participants with a resolved or chronic HBV infection are eligible if they are:
  • Negative for HBsAg and positive for hepatitis B core antibody [anti-HBc IgG or total anti-HBc Ab]. In addition, patients should be referred to a local hepatologist and treated as per local guidelines. or
  • Positive for HBsAg, but for > 6 months have had transaminases levels below ULN and HBV DNA levels below <100 IU/mL or below the detectable limit of locally available test kit (i.e., are in an inactive carrier state). In addition, patients must be receiving anti-viral prophylaxis for 2-4 weeks prior to study treatment.
  • Patients with HIV are only eligible for inclusion if they meet all the following criteria:
  • Demonstrated absence of HBV/ HCV co-infection
  • Undetectable viral RNA load for 6 months
  • CD4+ count of >350 cells/µL
  • No history of AIDS-defining opportunistic infection within the past 12 months
  • Stable for at least 4 weeks on the same anti-HIV medications
  • Patients must be willing to use protocol specified method of contraception during treatment with osimertinib and 6 weeks tafter the lost dose of osimertinib.
  • Females who are not abstinent (in line with the preferred and usual lifestyle choice of the patient) and intend to be sexually active with a male partner must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
  • Post-menopausal defined as aged 50 years or more and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
  • Women under 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution
  • Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
  • Male participants must be willing to use barrier contraception

Who cannot join

  • A potential subject who meets any of the following criteria will be excluded from participation in this study:
  • The patient has an acute gout attack, and medical history of gout or xanthinuria
  • The patient uses urate-lowering agents, azathioprine, 6-mercaptopurine, tioguanine
  • The patient uses potent inducers of UDP-glucuronosyltransferase (UGT) enzymes, such as rifampicin and carbamazepine
  • The patient uses prohibited co-medication: drugs that moderately or strongly inhibits or induces CYP3A4 or P-glycoprotein (P-gp)
  • The patient has received prior treatment with intrathecal chemotherapy
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  • The patient has moderate or severe hepatic dysfunction (Child Pugh B or C)
  • The patient has a significantly increased rate of uric acid production (such as in Lesch-Nyhan syndrome)
  • The patient is pregnant or lactating
  • The patient has been diagnosed with severe cardiovascular conditions (including history of myocardial infarction, stroke or instable angina pectoris, or congestive heart failure)
  • Any of the following cardiac criteria:
  • Mean resting corrected QT interval (QTc) > 470 msec, obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value.
  • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block.
  • Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as electrolyte abnormalities including: Hypokalaemia* ≥ CTCAE Grade 2 (*correction of electrolyte abnormalities should be documented prior to first dose), heart failure, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause Torsade de Pointes.
  • Creatinine >1.5 times ULN concurrent with creatinine clearance <50 ml/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN
  • Known galactose-intolerance, Lapp lactasedeficiency or glucose-galactose malabsorption
  • Involvement in the planning and/or conduct of the study (applies to both investigator staff and/or staff at the study site)
  • Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia and grade 2 prior platinum-therapy related neuropathy.
  • Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or active infection (e.g. patients receiving treatment for infection) including hepatitis C and human immunodeficiency virus (HIV), or active uncontrolled HBV infection.
  • o Screening for chronic conditions is not required.
  • Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib.
  • Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
  • Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
  • Bone marrow reserve (the use of granulocyte colony stimulating factor support, platelet transfusion and blood transfusions to meet these criteria is not permitted):
  • Absolute neutrophil count <1.5 x 109/L
  • Platelet count <100 x 109/L
  • Haemoglobin <90 g/L
  • Hepatic function
  • Alanine aminotransferase >2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases
  • Aspartate aminotransferase >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases
  • Total bilirubin >1.5 times ULN if no liver metastases or >3 times ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or liver metastases
  • History of hypersensitivity to active or inactive excipients of osimertinib or febuxostat, or drugs with a similar chemical structure or class to osimertinib or febuxostat.
  • Osimertinib dosage of less than 80 mg once daily.
  • Any concurrent and/or other active malignancy that has required systemic treatment within 2 years of first dose of osimertinib.
  • Major surgery within 4 weeks of the first dose of IP. Procedures such as placement of vascular access, biopsy via mediastinoscopy or biopsy via video assisted thoracoscopic surgery (VATS) are permitted.
  • Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of IP.
  • Judgement by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
  • Participation in another clinical study with an investigational product during the 4 weeks prior to Day 1. Patients in the follow-up period of an interventional study are permitted.
  • If a patient uses anticoagulants and the treating physician deems it unsafe or not feasible to temporarily interrupt this medication or to bridge oral anticoagulants with parenteral anticoagulation (i.e. LMWH) at the time of the lumbar puncture procedure, the patient will be excluded.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Netherlands2 sites, 2 recruiting

  • The Netherlands Cancer Institute

    Amsterdam

    Not yet recruiting

  • Maastricht UMC+

    Maastricht

    R van Geel, PharmD, PhD, +31 (0)43 38 71881, robin.van.geel@mumc.nl

    Recruiting

Other trials in Netherlands

About this study

Official title: Boosting Osimertinib Blood Brain Barrier Penetration in Patients With Epidermal Growth Factor Receptor Mutated Non-small Cell Lung Cancer

The goal of this proof-of-concept clinical study is to determine the effect of combining osimertinib with febuxostat on cerebrospinal fluid concentrations of osimertinib in patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC). The main question it aims to answer is: what is the effect of combining osimertinib with the ABCG2 inhibitor febuxostat on cerebrospinal fluid to unbound plasma osimertinib concentration ratio in patients with EGFR mutated NSCLC without central nervous system (CNS) metastases and without the ABCG2 34G>A single nucleotide polymorphism (SNP)?

Read the detailed description

One of the preferred first line treatment for metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) is osimertinib, a tyrosine kinase inhibitor (TKI). Despite the good intracranial efficacy of osimertinib compared with older-generation EGFR-TKIs, 10-20% of patients develop new or progressing central nervous system (CNS) metastases, the reason for which is unknown. Although the CNS penetration of osimertinib should be sufficient to reach therapeutic concentrations, drug efflux pumps in the blood brain barrier (BBB) could play a role in preventing therapeutic concentrations, especially in patients without baseline CNS metastases. In these patients the BBB is not compromised in contrast to patients with baseline CNS metastases, in whom a leaky BBB allows better penetration of osimertinib. As a result, microscopic CNS metastases then have the opportunity to grow.

Osimertinib is a substrate of drug transporters P-glycoprotein (P-gp; gene: ABCB1) and Breast Cancer Resistance Protein (BCRP) (ABCG2; gene: ABCG2), present in the BBB. Germline variations in these transporters influence intracerebral osimertinib efficacy. Patients without CNS metastases and with the ABCG2 34G>A single nucleotide polymorphism (SNP) have a 72% reduced risk of developing CNS metastases compared to other genotypes, potentially due to diminished osimertinib BBB-efflux, resulting in higher cerebrospinal fluid (CSF) penetration. This finding offers rationale to combine osimertinib with febuxostat, a strong selective ABCG2 transporter inhibitor, in order to enhance the intracerebral osimertinib concentration in patients without the ABCG2 34G>A SNP (~85% of patients).

The main trial endpoint is the change in the CSF to unbound plasma concentration ratio of osimertinib before and after co-administration with febuxostat.

Being tested
Osimertinib & febuxostat
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.

  • Osimertinib & febuxostatDrug

    Combining osimertinib with the ABCG2 inhibitor febuxostat to evaluate the effect on CSF concentrations of osimertinib

Study groups in NCT07485452
Study groupRoleWhat they receive
Combining osimertinib with febuxostat on cerebrospinal fluid concentration of osimertinibExperimentalDetermining the effect of combining osimertinib with ABCG2 inhibitor febuxostat on cerebrospinal fluid to unbound plasma osimertinib concentration ratio, in patients with EGFR mutated NSCLC without CNS metastases and without the ABCG2 34G>A SNP
Receives: Drug: Osimertinib & febuxostat

What is being measured

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

  1. Effect of combining osimertinib with febuxostat on osimertinib CSF:plasma ratio in patients with EGFR NSCLC without CNS metastases

    Determining the effect of combining osimertinib with the ABCG2 inhibitor febuxostat on osimertinib cerebrospinal fluid to plasma (CSF:plasma) concentration ratio, in patients with EGFR mutated NSCLC without central nervous system (CNS) metastases on brain MRI. Both CSF and plasma concentrations will be measured before and after combination of osimertinib with febuxostat.

    Measured: 22-25 days after start of combination osimertinib + febuxostat

Secondary outcomes (5)

  1. Effect on intracerebral osimertinib concentrations after combination with febuxostat

    Evaluating the extent by which febuxostat increases intracerebral osimertinib concentrations, by measuring osimertinib concentration in CSF before and after combination with febuxostat

    Measured: 22-25 days after start of concurrent treatment

  2. Effect on osimertinib plasma concentrations

    Assessing the effect of febuxostat on osimertinib plasma trough concentration in steady-state, by comparing concentrations before and after combination with febuxostat

    Measured: 22-25 days after start of combined treatment

  3. Plasma concentrations of AZ5104 and AZ7550

    Assessing the effect of febuxostat on AZ5104 and AZ7550 (i.e. active metabolites of osimertinib) steady-state trough concentrations, by comparing concentrations before and after combined use.

    Measured: 22-25 days after start of combined treatment

  4. CSF concentrations of AZ5104 and AZ7550

    Assessing the effect of febuxostat on AZ5104 and AZ7550 (i.e. active metabolites of osimertinib) concentrations in CSF, by comparing concentrations before and after combined use.

    Measured: 22-25 days after start of combined treatment

  5. Tolerability of osimertinib in combination with febuxostat

    Determining tolerability of osimertinib combined with febuxostat, by assessing adverse events according to CTCAE v5.0 criteria

    Measured: 22-25 days after start of combined treatment

Timeline

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

  1. First posted20 Mar 2026
  2. Study startJun 2026 (estimated)
  3. Primary completionJun 2027 (estimated)
  4. Study completionJun 2028 (estimated)

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
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
7 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07485452
Sponsor's protocol ID
OSIBBBOOST
Other IDs
2025-523033-26-00, 2025
Acronym
OSIBBBOOST
Status last verified
Jun 2026
First submitted
15 Jan 2026
Last updated
5 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Planchard D, Janne PA, Cheng Y, Yang JC, Yanagitani N, Kim SW, Sugawara S, Yu Y, Fan Y, Geater SL, Laktionov K, Lee CK, Valdiviezo N, Ahmed S, Maurel JM, Andrasina I, Goldman J, Ghiorghiu D, Rukazenkov Y, Todd A, Kobayashi K; FLAURA2 Investigators. Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC. N Engl J Med. 2023 Nov 23;389(21):1935-1948. doi: 10.1056/NEJMoa2306434. Epub 2023 Nov 8.

    PubMed 37937763

  • Veerman GDM, Boosman RJ, Jebbink M, Oomen-de Hoop E, van der Wekken AJ, Bahce I, Hendriks LEL, Croes S, Steendam CMJ, de Jonge E, Koolen SLW, Steeghs N, van Schaik RHN, Smit EF, Dingemans AC, Huitema ADR, Mathijssen RHJ. Influence of germline variations in drug transporters ABCB1 and ABCG2 on intracerebral osimertinib efficacy in patients with non-small cell lung cancer. EClinicalMedicine. 2023 Apr 13;59:101955. doi: 10.1016/j.eclinm.2023.101955. eCollection 2023 May.

    PubMed 37125403

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Osimertinib & febuxostat in people with Non-Small Cell Lung Cancer, run by Maastricht University Medical Center 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 30 inclusion and 39 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: looking for participants now, as of the sponsor's last update on 5 Jun 2026. 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?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Effect of combining osimertinib with febuxostat on osimertinib CSF:plasma ratio in patients with EGFR NSCLC without CNS metastases (time frame: 22-25 days after start of combination osimertinib + febuxostat). 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 NCT07485452, which also lists 2 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 5 Jun 2026.

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