NSCLC
Conditions
Interventions
Intervention group:Drug treatment
Sponsors
Shandong First Medical University and Shandong Academy of Medical Sciences (Shandong Cancer Hospital &Institute)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Age >= 18 years at the time of screening. A written informed consent should be obtained from the patient or his/her legally acceptable representative; 2. Histologically or cytologically documented Stage I to II NSCLC (American Joint Committee on Cancer Stage [Cancer Staging Manual, 9th Edition]), with clinical Stage I or II lymph node-negative (T1 to T3, N0, M0) disease and planned to receive definitive treatment with SBRT. In order to be eligible for this trial, patients should be: – Medically inoperable as determined by physician or; – Medically operable with patient’ refusal of surgery. 3. Planned SoC SBRT as definitive treatment (see Appendix E) using one of the following doses: – For peripheral tumors: 54 Gy total dose delivered in 3 fractions, 42 or 48 Gy total dose delivered in 4 fractions, 50 or 55 Gy total dose delivered in 5 fractions, or 50 or 60 Gy total dose delivered in 8 fractions; – For central tumors: 50 or 55 Gy total dose delivered in 5 fractions, or 50 or 60 Gy total dose delivered in 8 fractions. 4. Confirmation by the local laboratory that the tumor harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations including de novo T790M. Local EGFRm testing must be conducted using a validated test for NSCLC tumor tissue /plasma samples in an accredited laboratory in compliance with local regulations. A pre-existing EGFRm positive result based on plasma ctDNA is also 0 Clinical Study Protocol--Osimertinib V 1.0 24 (112) acceptable for patient eligibility provided that the result was obtained using a validated test in an accredited laboratory. 5. Tumor samples (optional): – Both unstained tumor slides and fresh biopsies are acceptable. 6. WHO/ECOG PS of 0, 1, or 2; 7. Patients with central or peripheral lesions are eligible. Central lesions are defined as a tumor within or touching the zone of the proximal bronchial tree, defined as a volume of 2 cm in all directions around the proximal bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus right, and left lower lobe bronchi). Patients with ultra-central tumors are NOT eligible. Ultra-central tumors are defined as PTV abutting or overlapping the trachea, mainstem bronchus, and/or esophagus; 8. Patients with a history of metachronus T1 to T3N0M0 (Stage I/II) NSCLC treated definitively with surgery only or SBRT only >1 year prior to enrollment are eligible. Patients with history of a metachronus early stage NSCLC (I - III), treated with curative intent >= 3 years prior to enrollment regardless of treatment modality, are eligible. Patients with a previous history of SBRT and/or other radiation therapy modalities to the lung are eligible provided additional radiation is deemed safe by the treating radiation oncologist and after consultation with the Study Physician; 9. Patients with synchronous NSCLC tumors are allowed when there is maximum of 2 intrathoracic lesions. Each lesion will be staged separately according to TNM system and identified in the electronic case report form (eCRF). Lesions must be treated with the same dose/fraction to each lesion and meet the Organ at Risk constraints identified in Appendix E. 10. The following staging studies must be done within 8weeks before enrollment: – An FDG-PET scan from at least the base of the skull to m
Exclusion criteria
Exclusion criteria: 1. Mixed small cell and non-small cell cancer; 2. Participation in another clinical study with an IP administered in the last 4 weeks; 3. Treatment with any of the following: – Preoperative (neoadjuvant) or adjuvant platinum-based or other chemotherapy for the disease under investigation; – Any prior anticancer or immunological therapy, including investigational therapy, for treatment of NSCLC for the disease under investigation; – Prior treatment with neoadjuvant or adjuvant EGFR-TKI; – Patients 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 B). 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. Treatment with an investigational drug within five half-lives of the compound or any of its related material, if known; 5. History of another primary malignancy except for – Malignancies treated with curative intent and adequate follow-up with no known active disease or have not required active treatment within the past 5 years – Adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease – Adequately treated carcinoma in situ, including Ta bladder tumors, without evidence of disease; 6. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE 5.0) grade 1 at the time of starting SBRT treatment. 7. 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. 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 electrolyte abnormalities including: – Hypokalaemia|* >= CTCAE Grade 2 – Serum/plasma magnesium 2.5 × ULN; – AST > 2.5 × ULN; – Total bilirubin >1.5 ×ULN or >3×ULN in the presence of documented Gilbert’s Syndrome (unconjugated hyperbilirubinaemia) – Creatinine >1.5 × ULN concurrent with creatinine clearance 1.5 ×
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PFS rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival; | — |
Countries
China
Contacts
Public ContactLigang Xing
Shandong First Medical University and Shandong Academy of Medical Sciences (Shandong Cancer Hospital &Institute)
Outcome results
None listed