resectable Stage II, IIIA and select IIIB non-squamous Non-Small Cell Lung Cancer MedDRA version: 20.0 Level: LLT Classification code 10079440 Term: Non-squamous non-small cell lung cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Tecentriq
Pharmaceutical Form: Concentrate and solvent for solution for infusion
Trade Name: Abraxane
Pharmaceutical Form: Powder and solvent for solution for infusion
Trade Name: CARBOp
Sponsors
Ruprecht-Karls University Heidelberg, Medical Faculty, repr. by HD University Hospital and its Commercial Managing Dir.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Willing and able to sign a written informed consent form (ICF ? Informed consent, patients age = 18-year-old including, signed and dated ? Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 ? Histologically confirmed NSCLC of non-squamous histology, cStage II, IIIA or select IIIB (T3N2 only); for T-status = T3 allowed; for N2 patients only IIIa1-3 Robinson classification allowed ? Deemed surgically resectable with curative intent by an attending thoracic surgeon after adequate staging including PET-CT ? Adequate lung and cardiac function for intended lung resection according to German S3 regulation ? Radiologically measurable disease as defined by response evaluation criteria in solid tumors RECIST v1.1 ? Sufficient availability of the tissue sample from primary tumor before start of neoadjuvant treatment ? Females of child-bearing potential must agree to use, and be able to comply with, effective contraception ( 1500/µl ? Platelet count = 100000/µl ? Hemoglobin = 9 g/dl (can be post-transfusion) ? International normalized ratio (INR) = 1.4 in patients not receiving anticoagulation; for patients receiving respective anticoagulation an INR =3.0 allowed ? Activated partial thromboplastin time (aPTT) = 1.5 times upper limit of normal (ULN) in patients not receiving anticoagulation; for patients receiving respective anticoagulation a PTT =2.5 ULN allowed ? Bilirubin 60 ml/min for subjects with creatinine levels > 1.5 ULN; for patients meeting the criterion of creatinine = 1.5 ULN also a calculated creatinine clearance of > 30 ml/min is mandatory Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Illness or condition that may interfere with a patient’s capacity to understand, follow, and/or comply with study procedures 2. Treatment in any other clinical trial within 30 days before screening. 3. NSCLC Stage cT4 4. NSCLC stage cN3 or cN2 IIIA4 (bulky or fixed multi-station N2 disease) according to Robinson classification 5. NSCLC of squamous cell histology 6. Any prior therapy for lung cancer (including systemic therapy, radiotherapy or major surgery) 7. Malignancies other than NSCLC within 5 years prior to study inclusion with the exception of malignancies with a negligible risk of metastasis or death (5-year OS > 90%) like localized prostate cancer, ductal carcinoma in situ, adequately treated carcinoma in situ of the cervix, Stage I uterine cancer or non-melanoma skin carcinoma 8. History of allogeneic tissue / solid organ transplant or allogeneic stem cell transplantation 9. Patients with active hepatitis B or C infections or a history of HIV infection. 10. Pregnant or lactating women 11. Active autoimmune disease or history of severe autoimmune disease or immunodeficiency or a syndrome that requires systemic steroids or immunosuppressive agents 12. The following exceptions are granted: o patients with vitiligo, eczema, lichen simplex or resolved childhood asthma/atopy o subjects requiring intermittent use of bronchodilators or local steroid injections o patients with hypothyroidism stable on hormone replacement 13. Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, and anti-tumor necrosis factor (anti-TNF) agents) within 2 weeks prior to Cycle 1, Day 1 (except low-dose steroids for adrenal failure or emesis prophylaxis) 14. History of idiopathic pulmonary fibrosis, interstitial lung disease, organizing pneumonia, drug-induced pneumonitis, or evidence of active pneumonitis on screening chest Computed Tomography (CT) scan. 15. Prior treatment with cluster of differentiation 137 (CD137) agonist or immune checkpoint blockade therapies, anti-programmed-death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibody 16. Live vaccine within 30 days prior to first dose of trial treatment 17. Cerebrovascular accident within the past 6 months 18. Severe infection or significant traumatic injury within the past 4 weeks 19. Clinically significant history of cardiovascular disease, including any of the following: o Myocardial infarction or unstable angina within the past 6 months o New York Heart Association class II, III-IV congestive heart failure o Poorly controlled cardiac arrhythmia despite medication, except rate-controlled atrial fibrillation 20. Known allergy or hypersensitivity to any component of the chemotherapy regimen 21. Patients who have been incarcerated or involuntarily institutionalized by court order or by the authorities, as well as patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess response in patients with NSCLC undergoing neoadjuvant ATEZOLIZUMAB investigational treatment in combination with Carboplatin and Nab-Paclitaxel before NSCLC curative intent surgery;Secondary Objective: To evaluate response rate by tumor size To evaluate response rate by PET-activity To evaluate event-free survival To evaluate overall survival Feasibility to proceed to surgery after neoadjuvant immunochemotherapy ;Primary end point(s): Response to neoadjuvant immunochemotherapy with ATEZOLIZUMAB, Carboplatin and Nab-Paclitaxel as determined by Major Pathologic Response (MPR) (=10% residual viable tumor cells) (pathologic regression grading according to Junker criteria) rate | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Response rate as determined by ? tumor size and ? lymph node size according to RECIST 1.1 criteria Response rate as determined by ? PET-activity (standardized uptake value [SUV]) Event-free survival (EFS) (event defined as relapse or death) - calculated from start of 1st cycle of neoadjuvant treatment follow-up for 24 months after end of treatment visit; end of treatment visit takes place 6 weeks after surgery Overall survival (OS) - calculated from start of 1st cycle of neoadjuvant treatment - follow-up for 24 months after end of treatment visit; end of treatment visit takes place 6 weeks after surgery Number of patients attaining surgery as planned | — |
Countries
Germany
Contacts
Public ContactThoraxchirurgie
Thoraxklinik Heidelberg gGmbH
Outcome results
None listed