Lung Cancer Non-small cell lung cancer
Conditions
Interventions
None listed
Sponsors
Universitair Medisch Centrum Groningen
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Provision of signed and dated, written informed consent. 2. Female and male subjects aged at least 18 years. 3. Subjects with histologically- or cytologically-documented non squamous NSCLC with a documented driver mutation (such as EGFR, ALK, ROS, BRAF, MET, RET, NTRK1-3, KRAS, NRG1, HER 2). 4. New (= 10mm in the longest diameter (except for pathological lymph nodes they must be >= 15mm in short axis) with computerized tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements. 9. Adequate hematologic and end organ function, defined by the following laboratory results obtained within =1500 cells/µL (without granulocyte colony-stimulating factor support) o WBC counts >2500/µL o Lymphocyte count >=500/µL o Platelet count >=100,000/µL (without transfusion) o Hemoglobin >=9.0 g/dL. Patients may be transfused or receive erythropoietic treatment to meet this criterion. o AST, ALT, and alkaline phosphatase = 30 mL/min. 10. Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: o Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments. o Women under 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) levels in the post-menopausal range for the institution. o Documentation of irreversible s
Exclusion criteria
Exclusion criteria: 1. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 14 days prior to inclusion of the study. 2. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti*PD-1, and anti*PD-L1 therapeutic antibodies. • Patients who have had prior anti*CTLA-4 treatment may be enrolled, provided the following requirements are met: o Minimum of 6 weeks from the last dose of anti*CTLA-4 o No history of severe immune related adverse effects from anti*CTLA-4 (CTCAE Grade 3 and 4). 3. CNS disease, treated brain metastases without the need for steroids are allowed. 4. Leptomeningeal disease. 5. Uncontrolled tumor-related pain. • Patients requiring pain medication must be on a stable regimen at study entry. • Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period. • Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment. 6. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). 7. Malignancies other than NSCLC within 3 years prior with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated with curative intent, ductal carcinoma in situ treated surgically with curative intent). 8. Pregnant and lactating women. 9. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins. 10. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cell products or any component of the atezolizumab formulation. 11. History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener*s granulomatosis, Sjögren*s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. • Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study. • Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study. 12. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. • History of radiation pneumonitis in the radiation field (fibrosis) is permitted. 13. Positive test for HIV. 14. Patients with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint: Response to treatment defined as Progression Free Survival (PFS) in months according to RECIST v1.1 and divided into the following subgroups of response: - primary resistance (PFS = 6 mo). Primary predictor variable: The change in level of ctDNA measured by ddPCR in blood between week 12 (end of chemotherapy) and week 18. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints: 1. Overall survival 2. Time to biological progression, defined as an increase of >= 30% in the levels of the specific mutation from the lowest value achieved, measured in ctDNA in blood using ddPCR. 3. Immune related adverse events (irAE). 4. Quality of life and symptom scores. | — |
Countries
Netherlands
Outcome results
None listed