Surveillance With PET/CT and Liquid Biopsies of Stage I-III Lung Cancer Patients After Completion of Definitive Therapy

Study Overview
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Brief Summary
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The purpose of this study is to improve early detection of treatable relapse of lung cancer and thereby improve survival and quality of life for the patients. The investigators will perform a multicenter, randomized controlled trial to 1) assess if surveillance with whole body Positron Emission Tomography combined with Computer Tomography (PET/CT) including the brain can increase the number of treatable relapses and 2) concurrently collect liquid biopsies for later analysis, potentially enabling even earlier and minimally invasive detection and characterization of relapse.

Official Title
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Surveillance With PET/CT and Liquid Biopsies of Stage I-III Lung Cancer Patients After Completion of Definitive Therapy; a Randomized Controlled Trial

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Diagnostic Test: Whole body 18F-FDG PET/CT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with non-small cell lung cancer (NSCLC), proven by cytology or histology Patient in clinical stages I-III Age≥ 18 years Performance status ≤ 2 at the time of referral to therapy Patient referred for definitive treatment (e.g. surgery, surgery followed by adjuvant chemotherapy, concomitant radio-chemotherapy, conventional or stereotactic radiotherapy or radiofrequency ablation). Patient has given his/her written informed consent before any specific procedure from protocol Exclusion Criteria: Patient, whose disease has progressed within the first 3 months after cancer treatment, e.g. confirmed progressive disease on CT. Persons deprived of liberty or under guardianship or curators Dementia, mental alteration, severe psychiatric disease or other circumstances that can compromise informed consent from the patient and/or adherence to the protocol and the monitoring of the trial Pregnant or breastfeeding women Patient participating in another interventional study during the surveillance period. This is only relevant for studies that might interfere with the intervention, whereas studies on late effects will not preclude participation in SUPE-R. Participation in protocols related only to initial treatment will not preclude participation in SUPE-R. Cases of doubt will be settled by the steering committee.

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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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter, randomized controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A, PET/CT<br>18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose positron emission tomography with computed tomography (FDG PET/CT) replacing computed tomography (CT) at months 6, 12, 18 and 24, otherwise as B with CT scan months 9, 15 and 21. Quality of life assessment and liquid biopsy every 3 months for later analysis. | Diagnostic Test: Whole body 18F-FDG PET/CT<br>* In the experimental arm (A), an FDG-PET/CT scan will replace the CT-scan at 6, 12, 18 and 24 months post-treatment. A standard CT-scan will be performed at 3, 9, 15 and 21 months post-treatment. All patients will be asked for a blood sample for liquid biopsy and to fill in a quality of life questionnaire, concurrently every 3 months.<br>|
| No Intervention: Control arm B<br>CT-scan and clinical evaluation every 3 months. Quality of life assessment and liquid biopsy at every 3 months for later analysis. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of relapses treatable with curative intent | As decided by multidisciplinary meetings | Until first detected relapse or 2 years after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to verified relapse | Relapse verified by histology or imaging combined with MDM review | From date of randomization until the date of first documented relapse assessed up to 24 months | 
| Overall survival | Death of any course or censoring | From date of randomization until the date of censoring or death from any cause, whichever came first, assessed up to 36 months | 
| Overall survival for patients with relapse | Death of any course or censoring | From randomization until 12 months after first detected relapse or until death (whichever comes first) | 
| Performance status at relapse | Performance status of study participants at relapse will be assessed using Eastern Cooperative Oncology Group (ECOG) performance status scale from grade 0 to grade 4, where grade 0 corresponds to a patient who is fully active, able to carry on all pre-disease performance without restriction and grade 4 is a patient who is completely disabled; cannot carry on any selfcare; totally confined to bed or chair. | From randomization until first detected relapse or 24 months | 
| Quality of life / QLQ-C30 | Quality of life will be assessed every 3rd month using a validated questionnaire, European Organisation for Research and Treatment of Cancer Quality of Life Questionaire Core Questionaire 30 (EORTC QLQ-C30). The questionaire is filled out by study participants at each control visit and patients score severity of a range of symptoms during the past week on a scale of 1 (Not at all) to 4 (Very much). | From randomization until first detected relapse or 24 months | 
| Quality of life / QLQ-LC13 | Quality of life will be assessed every 3rd month using a validated questionnaire, European Organisation for Research and Treatment of Cancer Quality of Life Questionair Lung Cancer 13 (EORTC QLQ-LC13). The questionaire is filled out by study participants at each control visit and patients score severity of a range of symptoms during the past week on a scale of 1 (Not at all) to 4 (Very much). | From randomization until first detected relapse or 24 months | 
| Quality of life / Raw score | From the results of QLQ-C30 and QLQ-LC13 a Raw Score (RS) is calculated (average of all scores) and Quality of Life is calculated as (RS - 1)/3 which outputs a value between 0 and 1, where 0 is a complete absence of symptoms and 1 is the maximum severity of all related symptoms. This will be used for calculation of QALY in the cost-effectiveness analysis. | From randomization until first detected relapse or 24 months | 
| Number of procedures to assess incidental findings | Procedures resulting from an incidental finding on a follow up scan | From randomization until 24 months or first detected relapse or until death (whichever comes first) | 
| Types of procedures to assess incidental findings | Invasive / non-invasive | From randomization until 24 months or first detected relapse or until death (whichever comes first) | 
| Adverse events due to invasive procedures done to assess incidental findings | For example: Bleeding, pneumothorax, hospital admission | From randomization until 24 months or first detected relapse or until death (whichever comes first) | 
| Cost-effectiveness analysis of intervention | Cost-effectiveness of the PET/CT regimen vs the CT regimen is assessed with the ICER (incremental cost-effectiveness ratio), i.e. the ratio of net health care costs to net QALYs ( quality-adjusted life years). Net health care costs are estimated as the health care costs difference between the two arms and net QALYs likewise. Health care costs are calculated from register-based information on health care consumption cumulated in 2-yrs follow-up (DRG-rates) supplemented by intervention costs based on project costs. The relevant cost data are available at Sundhedsdatastyrelsen using their research service. | From randomization until 24 months or 12 months after first detected relapse or until death (whichever comes first) | 
| Type of treatment after verification of relapse | Description of treatment - e.g. surgical, radiotherapy, stereotactic ablative body radiotherapy, medical treatment | From randomization until 12 months after first detected relapse or until death (whichever comes first) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Positron Emission Tomography Computed Tomography, X-Ray Computed Tomography, Liquid Biopsy, Quality of Life, Medical Oncology, Radiation Oncology, Follow-up