OCEANiC: A Phase II, Open-label, Multi-centre Clinical Trial of Osimertinib With or Without Adjuvant Chemotherapy Guided by Tumour NGS Co-mutation Status and ctDNA Detection in Patients With Stage IIA-IIIA EGFR-Mutant Non Small Cell Lung Cancer Following Complete Surgical Resection

ACTRN 12623000552684

Brief Summary

The purpose of this study is to investigate whether we can use co-mutation NGS profiling (looks for gene changes in your cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs tissuea group of cells that work together to perform a function) and circulating tumoura tissue mass that forms from groups of unhealthy cells (ct) DNA (looks for fragments of the tumour moving through the bloodthe red bodily fluid that transports oxygen and other nutrients around the body stream. These fragments are known as circulating tumour DNA (ctDNA) and carry genetic information) to determine which patients with EGFR mutant non small-cell lung cancer can safely avoid chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.

Intervention/Treatment

• Drug: Osimertinib.
• Platimun Doublet Chemotherapy.

Inclusion Criteria

1. Adults, aged 18 years or older, with histological diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of NSCLC. Patients with mixed small cell lung cancer histology are not eligible.
2. Stage IIA to IIIA NSCLC according to AJCC 8th edition.
3. Complete surgical resectionsurgical removal of tissue or part/all of an organ of the primary NSCLC is mandatory.
   • All gross tumour surgically removed at the end of surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence.
   • All surgical resection margins must be microscopically negative.
   • Resection may be accomplished by open or VATS techniques.
   • Surgery may consist of segmentectomies, lobectomya surgical procedure where a lobe of an organ (e.g. the lung) is removed, sleeve resection, bi-lobectomy or pneumonectomycomplete removal of affected lung based on the intraoperative findings with appropriate lymph nodea small lump or mass of tissue in your body sampling/mapping as determined by the surgeon. Patients who have only had wedge resections are not eligible.
4. Complete recovery from surgery at the time of registration. No more than 8 weeks may have elapsed between surgery and registration. Complete post-operative wound healing must have occurred following surgery.
5. Documented evidence of EGFR mutation (at any time since the initial diagnosis of NSCLC) known to be sensitive to osimertinib. These include exon 19 deletions, L858R (exon 21), G719X (exon 18), L861Q (exon 21), S768I (exon 20) and T790M (exon 20). Compound mutations involving any of the listed sensitising mutations are allowed.
6. ECOG Performance Status of 0 or 1 within 14 days prior to planned treatment start date.
7. Tumour tissue available from diagnostic biopsyremoval of a section of tissue to analyse for cancer cells or surgical specimena sample for investigating (e.g. blood, stools, urine, sputum etc.) for co-mutation testing.
8. Adequate organ system function within 14 days prior to planned treatment start date:
   • Bone marrowsoft, spongy tissue found in bones that makes blood cells function:
     1. Plateletssmall disc-shaped blood cells that clump together to form clots to stop bleeding more than or equal to 100 x 109/L.
     2. Absolute neutrophil count (ANC) more than or equal to 1.5 x 109/L.
     3. Haemoglobin more than or equal to 90 g/L.
   • Liver function:
     1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x upper limit of normal (ULN).
     2. Total bilirubin less than or equal to 1.5 x ULN or 3 x ULN in the presence of documented Gilbert’s Syndrome (unconjugated hyperbilirubinaemia).
   • Renal function:
     1. Measured Creatinine clearance greater than or equal to 45 mL/min can be determined using any of the following: 51Cr-EDTA, 99mTc-DTPA renography, 24-hour urine collection for creatinine clearance, Calculated creatinine clearance greater than or equal to 45 mL/min by the Cockcroft-Gault formula or Chronica long-lasting disease that changes slowly over time Kidneya pair of bean-shaped organs in the abdomen that are responsible for filtering excess water and waste products from the blood and converting them into urine to be removed from the body Disease Epidemiology Collaboration (CKD-EPI) formula.
9. MRI scan of the brain must be performed at any time between diagnosis and registration.
10. Baseline ECG with QTc <470ms and no clinically significant arrhythmias.
11. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.
12. Signed, written informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment..