Brain Metastases, Non-small Cell Lung Cancer, Quality of Life, Venous Thromboembolism
Conditions
Keywords
non-small cell lung cancer, immunotherapy, checkpoint inhibition, biomarkers, quality of life, real life patients
Brief summary
The LIFE study (Lung cancer, Immunotherapy, Frailty, Effect) is investigating the unselected 'real life' non-small cell lung cancer (NSCLC) population treated with immune checkpoint inhibition.
Detailed description
The era of immune checkpoint inhibition (ICI) has changed the treatment regimen for incurable non-small cell lung cancer. With that the hope of a more long-term survival has been introduced. ICI is given as standard therapy for selected NSCLC patients with incurable advanced or metastatic (stage IV) disease. For this group of patients clinical trial reports present a 3 year overall survival rate of around 30%. Checkpoint inhibition is also known as programmed death 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors and the PD-L1 tumor proportion score is currently the only clinically applicable biomarker used for this patient selection. New prognostic and predictive biomarkers are therefore warranted.The real life unselected NSCLC patient eligible for treatment with immunotherapy (check point inhibition) may be both older, with more comorbidity, more widespread disease and in poorer performance status than patients treated in clinical phase III trials. In this prospective single center study, clinical patient data, peripheral blood and baseline pre-treatment tumor biopsies are collected from NSCLC patients treated in any given treatment line with nivolumab, pembrolizumab or atezolizumab. Besides baseline samples consecutive blood samples will be collected for cytokine profiling and measurement of circulating tumor DNA (ctDNA) and micro RNA analysis. Baseline MRI of the brain screening for brain metastases and an extended CT-scan of thorax, abdomen and the lower extremities will be performed screening for venous thromboembolism (VTE). This along with comorbidity screening tools and quality of life assessments will provide detailed mapping of both patient and disease characteristics of potentially more frail patients including those with untreated brain metastases. By also registering immune related adverse events (irAE) prospectively in this study and doing additional blood samples in case of grade 3-4 toxicity, identification of biomarkers as predictors for effect and toxicity is durable. Hopefully this will contribute to more optimized treatment courses for those NSCLC patients to come.
Interventions
DIAGNOSTIC_TESTCT-scans extended
CT scans of thorax, abdomen and lower extremities are performed - screening for venous trombolisms at baseline and at 6 months in each patient. If VTE is diagnosed, medications according to guidelines will be administered.
DIAGNOSTIC_TESTMRI scan of the brain
MRI scan of the brain screening for brain metastases. If brain metastases are diagnosed - the possibility of giving radiotherapy along the course of ICI is discussed with the patient. In case of brain metastases consecutive MRI scans of the brain will be performed in order to follow the course (natural or post-radiotherapy) of the disease.
OTHERProspective registration of irAEs
irAEs are registered according to Common Terminology Criteria for Adverse Events version 4.0 by a medical doctor or trained experienced clinical nurse.
BEHAVIORALQuality of Life questionnaires
Participants fill out two Quality of Life questionnaires. The European Organization of Research and Treatment of Cancer, Quality of Life -30 questionnaire (EORTC QoL-30) and the European Questionnaire - 5 dimensions-5-level questionnaire (Euro EQ-5D-5L).
Sponsors
Odense University Hospital
University of Copenhagen
Odense Patient Data Explorative Network
Region of Southern Denmark
University of Southern Denmark
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years * Stage IV NSCLC or recurrent NSCLC. * Squamous or non-squamous histology * Any treatment-line - Independent of prior treatment * Candidate for checkpoint inhibitor (PD-1/PD-L1 targeting agents) immunotherapy * No previously known allergy to PD-1/PD-L1 targeting agents. * Able to give written consent
Exclusion criteria
* none
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with CTCAE 4.0 toxicity registered Immune related autoimmune events (irAE). | ICI will be given for a maximum of 24 months, and irAE registered up till one year post ICI treatment, which is anticipated to be within 4 years after of start inclusion. | Number of patients with CTCAE 4.0 toxicity registered according to age, comorbidity and predictive biomarkers. |
| Effect of checkpoint inhibition | ICI will be given for a maximum of 24 months, and follow-up is a maximum of one year post ICI, therefore is anticipated to be compleated within 4 years after start of inclusion. | Effect of ICI by calculating patients' overall median survival time. |
| Potential biomarkers for patient outcome including cDNA, mRNA and coagulation markers. | ICI will be given for a maximum of 24 months, and during follow-ip of one year post ICI treatment. Therefore it is anticipated to be compleated within 4 years after start inclusion | Investigations of blood samples stored in a biobank. These include cDNA, mRNA, acute phase reactants, markers of coagulation. |
| Best response of checkpoint inhibition | ICI will be given for a maximum of 24 months, and during follow-ip of one year post ICI treatment. Therefore it is anticipated to be compleated within 4 years after start inclusion. | Best response during ICI in patients, defined as radiologic response rates using CT evaluations (Recist 1.1 criteria) combined with clinical status during ICI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Quality of Life in patients at baseline and at follow-up using EORTC QoL-30. | ICI will be given for a maximum of 24 months, and the follow-up period is one year, therefore completion is anticipated to be within 4 years after start inclusion. | Questionnaires of EORTC-Quality of Life-30 (EORTC QoL-30). |
| The Quality of Life in patients at baseline and at follow-up using European EQ-5D-5L). | ICI will be given for a maximum of 24 months, and the follow-up period is one year, therefore completion is anticipated to be within 4 years after start inclusion. | Evaluating Quality of Life using the European Quality of life - 5 Dimensions - 5 Levels questionnarie (Euro EQ-5D-5L) at baseline, during treatment and at follow-up. |
| Registration of venous thromboembolism (VTE) during treatment with ICI. | ICI will be given for a maximum of 24 months, which is anticipated to be within 4 years after start inclusion | Registration of VTE during treatment with ICI using expanded CT scans at baseline/6 months. |
Countries
Denmark
Outcome results
None listed