LIFE - Lung Cancer, Immunotherapy, Frailty, Effect

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Quality of Life; Venous Thromboembolism; Non-small Cell Lung Cancer; Brain Metastases
• Intervention / Treatment: Diagnostic test: CT-scans extended; Diagnostic test: MRI scan of the brain; Other: Prospective registration of irAEs; Behavioral: Quality of Life questionnaires

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.

• Study Type: Observational
• Enrollment (Actual): 150

Contacts and Locations

Study Locations

• Denmark
  • Odense, Denmark, 5000
    • Department of Oncology, Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

A total of 150 patients with incurable advanced (stage III A-C) or metastatic (stage IV) non-small cell lung cancer eligible for treatment with ICI at a Danish Hospital (Odense, Denmark). All possible treatment lines are allowed. ICI administered as nivolumab, pembrolizumab or atezolisumab.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Prospective arm; 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; 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 test: MRI 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.; Other: Prospective 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.; Behavioral: Quality 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).

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: University of Southern Denmark
• Collaborators: Odense University Hospital; University of Copenhagen; Region of Southern Denmark; Odense Patient Data Explorative Network
• Investigators: Principal Investigator: Birgitte Bjørnhart, MD, University of Southern Denmark

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2018
• Primary Completion (Anticipated): November 8, 2022
• Study Completion (Anticipated): November 8, 2022

Study Registration Dates

• First Submitted: March 1, 2019
• First Submitted That Met QC Criteria: March 8, 2019
• First Posted (Actual): March 12, 2019

Study Record Updates

• Last Update Posted (Actual): May 24, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: immunotherapy; biomarkers; quality of life; non-small cell lung cancer; checkpoint inhibition; real life patients
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Embolism and Thrombosis; Central Nervous System Neoplasms; Nervous System Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms; Thromboembolism; Venous Thromboembolism
• Other Study ID Numbers: BBjornhart

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No