Osimertinib to Suppress the Progression of Remaining GGN for EGFR Mutation-positive Stage IB-IIIA Lung Adenocarcinoma

Exclusion Criteria

• •1. Regression of synchronous GGN after adjuvant chemotherapy prior to osimertinib
• •2. Past history of postoperative ALI/ARDS or pneumonia during recovery period
• •3. Currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4 (at least 3 week prior) (Appendix C). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4.
• •4. 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 including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
• •5. 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.
• •6. 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. Whenever QTc, is mentioned in this document, this refers to correction e made by Fridericia formula (QTcF),
• •* 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 \< lower limit of normal (LLN); Serum/plasma magnesium \< LLN; Serum/plasma calcium \< LLN) , 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 Torsades de Pointes
• •7. 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.
• •8. Inadequate bone marrow reserve or organ function (as demonstrated by any of the following laboratory values:
• •* Absolute neutrophil count \<1.5 x 109/L;
• •* Platelet count \<100 x 109/L;
• •* Haemoglobin \<90 g/L;
• •* Alanine aminotransferase \>2.5 times 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;
• •* Serum 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.
• •9. Women who are breast-feeding
• •10. Males and females of reproductive potential who are not using and effective method of birth control and females who are pregnant or breastfeeding or have a positive (urine or serum) pregnancy test prior to study entry.
• •11. Involvement in the planning and conduct of the study (applies to AstraZeneca staff or staff at the study site).
• •12. History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib.