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New treatment option for Non-Small Cell Lung Cancer
Official title Boosting Osimertinib Blood Brain Barrier Penetration
ClinicalTrials.gov ID: NCT07485452
What this study is testing
What is Osimertinib & febuxostat?
Osimertinib & febuxostat is an investigational medicine, being studied as a potential treatment for non-small cell lung cancer.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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)?
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join 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...
- 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.
You likely can't join 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
See the full eligibility criteria
Who can 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...
- 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...
- 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)...
- 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...
- 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...
- 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
What rules you out
- 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...
- Creatinine \>1.5 times ULN concurrent with creatinine clearance \ 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...
- 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...
- 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 treatment 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...
The study team makes the final eligibility decision.
Where it's taking place
- Amsterdam, Netherlands
- Maastricht, Netherlands
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Amsterdam, Netherlands; Maastricht, Netherlands. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.