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Study of osimertinib and febuxostat to improve drug delivery in patients with EGFR-mutated non-small cell lung cancer without brain metastases

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What is this trial about?

A plain-language summary of the goals, design and what participants do

This study focuses on individuals with Non-Small Cell Lung Cancer that has spread to other parts of the body and contains a specific change in the EGFR gene. The research aims to determine if adding febuxostat to the current treatment can help more of the medication osimertinib reach the brain. This is important because the blood-brain barrier, a protective layer that prevents many substances from entering the brain, can sometimes block medicine from working effectively in that area.

During the study, participants will continue to take their regular dose of osimertinib and will also begin taking febuxostat. To see how well the drugs are working, researchers will measure the amount of the medication in both the blood and the cerebrospinal fluid, which is the clear liquid that surrounds the brain and spinal cord. These measurements will be taken before and after the addition of the second medication to compare the levels.

The research process

The trial runs in 2 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
<b>medication administration</b>
The treatment involves taking two types of tablets orally. The first is osimertinib, provided in 80 mg film-coated tablets. The second is febuxostat, provided in 80 mg film-coated tablets.
These medications are taken as part of a combination therapy to study how the amount of osimertinib in the cerebrospinal fluid (the fluid surrounding the brain and spinal cord) compares to the amount in the blood.
Step 2
<b>measurements and monitoring</b>
Measurements of osimertinib concentrations are taken in both the cerebrospinal fluid and the plasma (the liquid part of the blood).
These measurements occur both before and after the addition of febuxostat to the osimertinib regimen.
The levels of specific substances, known as AZ5104 and AZ7550, are also measured in the plasma and cerebrospinal fluid.
Any adverse events, which are side effects or unwanted medical occurrences, are recorded and monitored throughout the process.

Who can join the trial?

15 criteria

You must be at least 18 years old.
You must have a confirmed diagnosis of metastatic nonsquamous non-small cell lung cancer (NSCLC), which is a type of lung cancer that has spread to other parts of the body.
Your cancer must have a specific genetic change called an EGFR mutation (specifically ex19del or ex21 L858R).
You must be currently taking the medicine osimertinib as part of your regular care.
Your cancer must be stable (not growing or spreading) or getting better based on imaging tests like CT scans. However, if your cancer is progressing, you may still join if your doctor believes it is appropriate to continue the medicine for at least one month.
You must not have any cancer spread to the central nervous system (CNS), such as the brain, as shown on a brain MRI.
You must not have a specific genetic variation known as the ABCG2 34G>A SNP.
You must have a good performance status (ECOG-PS) of 0 or 1, which means you are generally able to carry out daily activities and light work with little or no restriction.
If you have Hepatitis B (HBV), you must meet specific requirements, such as not having Hepatitis C (HCV) or HIV, having a very low amount of the virus in your blood, and having stable liver enzyme levels.
If you have HIV, you must not have Hepatitis B or Hepatitis C, have an undetectable amount of the virus in your blood for at least 6 months, have a CD4+ count (a type of immune cell) greater than 350 cells/µL, and have no history of serious infections related to AIDS in the last 12 months.
You must agree to use effective contraception (methods to prevent pregnancy) during the study and for 6 weeks after the last dose. Women may need to provide proof they are not pregnant or are post-menopausal, while men must use barrier methods like condoms.
You must be able and willing to sign an informed consent form, which is a document where you agree to participate after understanding all the details of the study.
You must be able and willing to have extra blood samples taken to monitor the levels of medicine in your body.
You must be able and willing to undergo two lumbar punctures, which is a procedure used to collect cerebrospinal fluid (CSF)—the clear liquid that surrounds your brain and spinal cord.
You must follow the official medical guidelines and rules for using osimertinib.

Who cannot join the trial?

28 criteria

Having an acute gout attack, which is sudden and severe joint pain and swelling, or a history of gout or xanthinuria, a condition where there is a low level of xanthine in the urine.
Having previously received intrathecal chemotherapy, which is medicine injected directly into the fluid surrounding the brain and spinal cord.
Having moderate or severe hepatic dysfunction, meaning the liver is not working properly, categorized as Child Pugh B or C.
Having a significantly high rate of uric acid production, such as in Lesch-Nyhan syndrome, a rare genetic disorder.
Being pregnant or breast-feeding.
Having severe cardiovascular conditions, including a history of myocardial infarction (heart attack), stroke, unstable angina pectoris (chest pain that is unpredictable and severe), or congestive heart failure (a condition where the heart cannot pump blood effectively).
Using urate-lowering agents (medicines to reduce uric acid), azathioprine, 6-mercaptopurine, or tioguanine.
Being part of the staff involved in planning or running the study.
Using anticoagulants (blood thinners) if the doctor decides it is unsafe to stop them or switch to a different type of injection, such as LMWH, before the lumbar puncture (a procedure where a needle is inserted into the spine to collect fluid).
Having any unresolved toxicities (side effects) from previous treatments that are higher than grade 1, meaning they are more than mild, except for alopecia (hair loss) or certain nerve issues called neuropathy.
Having severe or uncontrolled systemic diseases, such as uncontrolled hypertension (high blood pressure), active bleeding diatheses (a tendency to bleed easily), or an active infection like hepatitis C, HIV, or HBV (Hepatitis B).
Participating in another clinical study using a new experimental medicine within the 4 weeks before starting this study.
Having refractory nausea and vomiting (nausea that does not go away), chronic stomach and intestinal diseases, an inability to swallow the medicine, or having had significant bowel resection (surgery to remove part of the intestine).
A history of interstitial lung disease (scarring of the lung tissue), drug-induced interstitial lung disease, or radiation pneumonitis (lung inflammation caused by radiation) that required steroid treatment.
Taking a dose of osimertinib that is less than 80 mg once daily.
Having any other active malignancy (cancer) that required treatment within the last 2 years.
Having major surgery within 4 weeks of the first dose of the study medicine.
Receiving radiotherapy (radiation treatment) to more than 30% of the bone marrow or using a wide area of radiation within 4 weeks of the first dose.
If the doctor believes the patient cannot follow the study rules and requirements.
Having specific heart rhythm issues, such as a QTc interval (a measurement of the heart's electrical timing) greater than 470 msec, or abnormalities like complete left bundle branch block or heart block.
Having factors that increase the risk of heart rhythm problems, such as electrolyte abnormalities (imbalances in body salts) like hypokalaemia (low potassium levels), or a family history of long QT syndrome.
Using medicines that affect certain enzymes in the liver, such as rifampicin or carbamazepine.
Having inadequate bone marrow reserve, which is measured by low levels of neutrophils (white blood cells that fight infection), platelets (cells that help blood clot), or haemoglobin (the part of red blood cells that carries oxygen).
Having impaired liver function, indicated by high levels of alanine aminotransferase, aspartate aminotransferase, or total bilirubin in the blood.
Having impaired kidney function, indicated by high creatinine levels or low creatinine clearance (how well the kidneys filter waste).
Using any other medicines that are not allowed in this study.
Having a history of hypersensitivity (allergic reaction) to the ingredients in osimertinib or febuxostat.
Having galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption (conditions that make it hard for the body to digest certain sugars).

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Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
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Rotterdam, The Netherlands
University Hospital Maastricht
Verified
Maastricht, The Netherlands

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Investigated drugs

Osimertinib
is a medication used to treat certain types of lung cancer. In this study, it is being studied to see how well it can reach the brain to treat cancer cells.
Febuxostat
is a medication typically used to manage high levels of uric acid. In this trial, it is being used to help more of the cancer medication reach the brain.

What is already known about the treatment

Osimertinib
This medication is taken orally in the form of a film-coated tablet and is commonly used to treat a specific type of advanced lung cancer. It belongs to a class of drugs called tyrosine kinase inhibitors, which work by blocking specific proteins that help cancer cells grow and divide. By targeting these mutated signals at a molecular level, the drug helps to slow down the progression of the disease.
Febuxostat
This medicine is administered by mouth as a film-coated tablet and is widely used in medical practice to manage gout by lowering uric acid levels in the blood. It works by blocking an enzyme in the body that is responsible for producing uric acid, thereby preventing the buildup of crystals that cause pain. In the context of this study, it is being investigated for its ability to help other medications reach different parts of the body more effectively.

Investigated diseases

Non-small cell lung cancer - This is a type of cancer that starts in the cells of the lungs. It is the most common form of lung cancer. The disease often begins in the airways or the lung tissue itself. As it progresses, cancer cells can grow and spread to other parts of the body. In certain cases, it is driven by specific changes in the cells' genetic makeup.