None listed
Conditions
Interventions
Drug : Neoadjuvant therapy
-Osimertinib 80mg once a day(QD) oral(PO)
-If there is no disease progression or unacceptable toxicity, treatment is performed for 2cycles at 1 cycle (28 days) interval
Adj
Sponsors
Yonsei University Health System, Severance Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 18 years and older 2. Provision of informed consent prior to any study specific procedures 3. Histologically or cytologically confirmed NSCLC(non small cell lung cancer) , performed on a biopsy 4. Documented activating EGFR mutation (Exon 19 deletion or L858R) 5. Positron emission tomography (PET)-computed tomography (CT) within the last 60 days showing radiographic stage I to IIIa lung cancer (mediastinal staging biopsy is allowed but not required) 6. Brain magnetic resonance imaging (MRI) (or CT if contraindication to MRI) within the last 60 days showing no evidence of metastatic disease 7. Documentation that the patient is a candidate for surgical resection of their lung cancer by certified surgeon 8. Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria 9. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1 10. All toxicity from previous chemotherapy, radiation therapy, or surgical procedures according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 recovered to Grade 1 . 11. Patients may receive supplements to meet this requirement this requirement - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3,000/mcL - Hemoglobin >= 9 g/dL, with no blood transfusions in the 28 days prior to study entry - Absolute neutrophil count > 1,500/mcL - Platelets > 100,000/mcL - Creatinine = 50 mL/min/1.73 m2 for patients with creatinine levels =< 1.5 x upper limit above institutional normal 12. Ability to swallow oral medications 13. Women of childbearing potential (WoCBP) must have a negative serum pregnancy test and agree to use highly effective contraception, during the study and for 90 days following the last dose of osimertinib 14. Women NOT of childbearing potential: women who are permanently or surgically sterilized or postmenopausal - Permanent sterilization includes hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy but excludes bilateral tubal occlusion; tubal occlusion is considered a highly effective method of birth control but does not absolutely exclude possibility of pregnancy; (the term occlusion refers to both occluding and ligating techniques that do not physically remove the oviducts) - Women who have undergone tubal occlusion should be managed on trials as if they are of WoCBP (e.g. undergo pregnancy testing etc., as required by the study protocol) 15. Women will be considered postmenopausal if they are amenorrhoeic for 12 months without an alternative medical cause; the following age-specific requirements apply: - Women under 50 years old will be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle-stimulating hormone levels in the postmenopausal range - Women over 50 years of age will be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatments 16. Acceptable contraception methods are: - Total sexual a
Exclusion criteria
Exclusion criteria: 1. Leptomeningeal carcinomatosis or other central nervous system (CNS) metastases 2. Stage IIIB, or distant metastases (including malignant pleural effusion) identified on PET-CT scan or biopsy 3. 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 4. History of confirmed, corneal ulceration 5. Patients who are known to be serologically positive for human immunodeficiency virus (HIV) 6. Active second malignancy, i.e. patient known to have potentially fatal cancer present for which he/she may be (but not necessarily) currently receiving treatment; patients with a history of malignancy that has been completely treated, with no evidence of that cancer currently, are permitted to enroll in the trial provided all chemotherapy for prior malignancy was completed > 12 months prior and/or bone marrow transplant > 2 years prior 7. Patients who are currently receiving treatment with contraindicated corrected QT interval (QTc) prolonging medications or potent CYP3A4 inducers, if that treatment cannot be either discontinued or switched to a different medication prior to first day of study treatment 8. 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 heart failure, electrolyte abnormalities (including: Serum/plasma potassium 2.5 times 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; - Serum creatinine >1.5 times ULN concurrent with creatinine clearance 1.5 times ULN. 10. Treatment with prohibited medications (concurrent anticancer therapy including chemotherapy, radiation, hormonal treatment [except corticosteroids and megesterolacetate], or immunotherapy) =< 14 days prior to treatment with osimertinib 11. Prior treatment with osimertinib or other drugs that target EGFR mutant non-small cell lung cancer (including erlotinib, afatinib, gefitinib, rocelitinib) 12. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hype
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rage (ORR) | — |
Secondary
| Measure | Time frame |
|---|---|
| Pathological response rate;Progression Free Survival (PFS);Overall survival (OS);Ratio of inability to resection (operational to non-surgical conversion rate);Safety;Exploratory analysis (Single cell RNA-seq);??? ?? (PBMC) | — |
Countries
Korea, Republic of
Contacts
Public ContactYuri Kang
Yonsei University Health System, Severance Hospital
Outcome results
None listed