LIFE - Lung Cancer, Immunotherapy, Frailty, Effect

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Impact of Age and Comorbidity on Effect of Treatment, Adverse Effects and Quality of Life in Danish Lung Cancer Patients Receiving Immunotherapy

Conditions
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Quality of Life, Non-small Cell Lung Cancer, Brain Metastases, Venous Thromboembolism

Intervention / Treatment
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* Diagnostic Test: CT-scans extended
* Diagnostic Test: MRI scan of the brain
* Other: Prospective registration of irAEs
* Behavioral: Quality of Life questionnaires


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Prospective arm<br>Quality of Life questionnaires EORTC-QoL30 and Euro EQ-5D-5L questionnaires are distributed. Blood samples are collected consecutively during ICI and at a follow-up period of one year. CT-scans extended of thorax, abdomen and the lower extremities are performed at baseline and at 6 months. 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.Prospective registration of irAEs are registered during ICI and for one year of follow-up.Enrolment period 1th of April 2018- 31th of April 2021. | Diagnostic Test: CT-scans extended<br>* 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.<br>Diagnostic Test: MRI scan of the brain<br>* 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.<br>Other: Prospective registration of irAEs<br>* irAEs are registered according to Common Terminology Criteria for Adverse Events version 4.0 by a medical doctor or trained experienced clinical nurse.<br>Behavioral: Quality of Life questionnaires<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with CTCAE 4.0 toxicity registered Immune related autoimmune events (irAE). | Number of patients with CTCAE 4.0 toxicity registered according to age, comorbidity and predictive biomarkers. | 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. | 
| Effect of checkpoint inhibition | Effect of ICI by calculating patients' overall median survival time. | 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. | 
| Potential biomarkers for patient outcome including cDNA, mRNA and coagulation markers. | Investigations of blood samples stored in a biobank. These include cDNA, mRNA, acute phase reactants, markers of coagulation. | 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 | 
| Effect of checkpoint inhibition | Effect of ICI by calculating patients' median progression free survival time. | 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 of checkpoint inhibition | Best response during ICI in patients, defined as radiologic response rates using CT evaluations (Recist 1.1 criteria) combined with clinical status during ICI. | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Registration of venous thromboembolism (VTE) during treatment with ICI. | Registration of VTE during treatment with ICI using expanded CT scans at baseline/6 months. | ICI will be given for a maximum of 24 months, which is anticipated to be within 4 years after start inclusion | 
| The Quality of Life in patients at baseline and at follow-up using EORTC QoL-30. | Questionnaires of EORTC-Quality of Life-30 (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. | 
| The Quality of Life in patients at baseline and at follow-up using European EQ-5D-5L). | 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. | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunotherapy, non-small cell lung cancer, checkpoint inhibition, biomarkers, quality of life, real life patients