stage IV EGFR mutated non-small cell lung cancer metastatic lung cancer with a mutation in the EGFR gene
Conditions
Interventions
Part I: Within 3 weeks after results of the EGFR mutation and within 2 weeks after discussion with the surgeon, patients will undergo resection of an easily accessible metastasis. 
Surgery will be performed with local anaesthesia if possible, otherwise general anaesthesia will be used. The surgery will be performed by an experienced surgical team and with a perioperative pain ma
Patients will start with osimertinib 7 days after the resection. 
Part II: Within 2 weeks after discussion in the multidisciplinary meeting, patients will undergo a resection of the metastasis. The largest resectable site will be chosen to be resected, taking into a
Surgery will be performed under general anesthesia, by an experienced thoracic surgery team and with a perioperative pain management to the discretion of the treating medical team. Before start of sur
Sponsors
Antoni van Leeuwenhoek (AVL)
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Written informed consent obtained before any study-specific procedures are conductedMale or female, =18 years of age.Histologically or cytologically confirmed adenocarcinoma of the lung.Documented EGFR exon 19 deletion or exon 21 L858R mutation, confirmed by tumor biopsy or plasma using ctDNA. Metastatic disease not amenable to curative treatment at the time of study screeningPresence of at least one tumor lesion = 2 cm, deemed potentially resectable by a surgeon Patients must be able to undergo surgical resection of part of this tumor lesionECOG/WHO performance status of 0 or 1 at screeningAdequate hematology and coagulation statusHb > 5.5 mmol/L Note: Red blood cell transfusions are allowed to increase the Hb at investigator’s discretion Platelet count > 75 x 109/L PTT < 1.5 x ULN APTT < 1.5 x ULN PT-INR = 1.5 on the day of surgery in patients using coumarines Patients with adequate organ function Adequate liver function: Total bilirubin < 3 x ULN (except in case of documented Gilbert’s disease) Adequate renal function: Creatinine < 3 x ULN Creatinine clearance (calculated by Cockcroft) > 45 mL/min Inclusion criteria specific for part I: Osimertinib naïve Presence of an easily resectable tumor lesion, for example (but not limited to) cervical or axillary lymph node, cutaneous metastasis or pulmonary metastasis resectable by wedge resection surgery. Resectability will be assessed by a qualified surgeon. Inclusion criteria specific for part II: Patients must have been treated with osimertinib for at least 3 months but no longer than 6 months before surgery.
Exclusion criteria
Exclusion criteria: Known bleeding disorders (e.g., hemophilia) or history of bleeding complications after biopsies, dental procedures or surgeries. Use of anti-coagulant medication, including coumarines, platelet function inhibitors, heparins (including LMWHs) and direct oral anticoagulants (DOACs), unless medication can be safely stopped or counteracted. Comorbid conditions that pose an increased surgical risk, such as (but not limited to) significant cardiac disease, limited pulmonary function or, active infectionUnstable brain metastases (growth of new lesions, the enlargement of existing lesions, or the spread to other areas of the brain) and/or symptomatic brain metastases.Active secondary malignancy, except for superficial skin malignancies.Prior radiation on the lung tumor or metastasis intended for resection. Exclusion criteria specific for part II:Progressive disease during osimertinib treatmentOsimertinib dose reduction
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The study is feasible (primary endpoint) in case 16 of 20 included patients in part II restart osimertinib 7 days after surgery and the interruption of osimertinib is not longer than 10 days. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary study parameters/endpoints Safety (according to CTCAE version 5.0) and complications (according to the standardized Clavien-Dindo classification of surgical complications) for both PART I and II.Other study parameters To study the mechanism of MRD and how it leads to osimertinib resistance. Also to see if the occurrence of MRD is random or that the same MRD occurs in patient and PDX models. To see if there are immune infiltrates which predict a response to TIL. | — |
Countries
Netherlands
Contacts
Public ContactSK Badrising
Antoni van Leeuwenhoek (AVL)
Outcome results
None listed