Boosting Osimertinib Blood Brain Barrier Penetration

Recruiting now · Phase 2

Conditions studied: Non-Small Cell Lung Cancer

In brief

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)?

Key facts

Study ID

NCT07485452

Run by

Maastricht University Medical Center

People needed

7

Starts

2026-06-01

Expected to finish

2028-06-01

Last updated by the study team

2026-06-05

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• 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.

You may not qualify if…

• 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
• 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

Where it is running

• Maastricht UMC+ — Maastricht, Netherlands (enrolling)
• The Netherlands Cancer Institute — Amsterdam, Netherlands

Full record on ClinicalTrials.gov

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