Clinical trial NCT03870464: LIFE - Lung Cancer, Immunotherapy, Frailty, Effect
Official title: The Impact of Age and Comorbidity on Effect of Treatment, Adverse Effects and Quality of Life in Danish Lung Cancer Patients Receiving Immunotherapy
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Non-small Cell Lung Cancer
Quality of Life
Brain Metastases
Venous Thromboembolism
Keywords: non-small cell lung cancer
immunotherapy
checkpoint inhibition
biomarkers
quality of life
real life patients
Lead sponsor: University of Southern Denmark
Sponsor class: OTHER
Collaborators: name: Odense University Hospital
name: University of Copenhagen
name: Odense Patient Data Explorative Network
name: Region of Southern Denmark
First posted: 2019-03-12
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of patients with CTCAE 4.0 toxicity registered Immune related autoimmune events (irAE).
timeFrame: 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.
measure: Effect of checkpoint inhibition
timeFrame: 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.
measure: Potential biomarkers for patient outcome including cDNA, mRNA and coagulation markers.
timeFrame: 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
measure: Effect of checkpoint inhibition
timeFrame: 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.
measure: Best response of checkpoint inhibition
timeFrame: 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 outcomes:
measure: Registration of venous thromboembolism (VTE) during treatment with ICI.
timeFrame: ICI will be given for a maximum of 24 months, which is anticipated to be within 4 years after start inclusion
measure: The Quality of Life in patients at baseline and at follow-up using EORTC QoL-30.
timeFrame: 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.
measure: The Quality of Life in patients at baseline and at follow-up using European EQ-5D-5L).
timeFrame: 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.
Other outcomes:
Locations:
city: Odense
country: Denmark
facility: Department of Oncology, Odense University Hospital
Study officials:
affiliation: University of Southern Denmark
name: Birgitte Bjørnhart, MD
role: PRINCIPAL_INVESTIGATOR
References: