Addition of Radiotherapy to Standard Medical Treatment for Stage IV NSCLC

Study Overview
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Brief Summary
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The hypothesis for this study is that addition of a moderate dose of radiotherapy to the primary tumor and mediastinal nodes after three months of medical treatment could reduce the tumor burden, partly as an abscopal effect, and thereby improving quality of life and possible also prolonging survival for stage IV NSCLC.

Detailed Description
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Primary objective: To assess whether the addition of radiotherapy to the remaining thoracic tumor burden following standard medical treatment results in a superior quality of life measured with lung cancer symptom scale (LCSS) in patients with stage IV non-small cell lung cancer. The comparison will be made at three months after randomization. Secondary objectives: Overall survival, progression-free survival, toxicity and longitudinal quality of life measurements. Design: Multicentre, randomized, phase III trial. Patients will be registered for the study up-front but randomization will be performed after evaluation of response, three months after initiating medical treatment with chemotherapy/ chemo-immunotherapy or immunotherapy. Randomization will be to thoracic radiotherapy or follow-up (1:1).

Official Title
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Multicentre Phase III Study: Addition of Radiotherapy to Standard Medical Treatment for Stage IV NSCLC

Conditions
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Radiotherapy, Non Small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer, Quality of Life

Intervention / Treatment
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* Radiation: Thoracic radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological or cytological confirmed non-small cell lung cancer (NSCLC) Stage IV disease Previously untreated disease (before first line treatment) No symptomatic brain metastases Performance status (WHO) 0-2 FEV1 (forced expiratory volume one second) ≥ 1 L or >40% of predicted Written informed consent Life expectancy ≥ 12 weeks Platelet count ≥ 100,00/mm3 Hemoglobin ≥ 10 g/dl WBC (White blod cells) ≥ 3,000/mm3 Kidney function allowing chemotherapy Patients scheduled for standard platinum based chemotherapy, chemo-immunotherapy or immunotherapy Willing and able to comply with study treatment Exclusion Criteria: Requirement for daily supplemental oxygen Second primary malignancy within 3 years, except for any of the following which can be included even if diagnosed within the past 3 years: Carcinoma in situ of the cervix, nonmelanoma skin cancer, history of low-grade (Gleason score ≤ 6) localized prostate cancer, definitely treated stage I breast cancer, other malignancy that was diagnosed and definitely treated ≥ 3 years ago with no subsequent evidence of recurrence Concurrent severe and/or uncontrolled medical condition, including any of the following: Angina pectoris Congestive heart failure within the past 3 months, unless LVEF (left ventricular ejection fraction) > 40% Myocardial infarction within the past 6 months Clinically significant infection Psychiatric illness or social situation that would limit compliance with study requirements EGFR (epidermal growth factor receptor) mutation or ALK (anaplastic lymphoma kinas) - rearrangement detected

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicentre randomized phase 3 trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: A: Standard of care<br>Normal standard of care and follow-up. | |
| Experimental: B: Thoracic radiotherapy<br>Addition of thoracic radiotherapy to 36 Gy after medical treatment. | Radiation: Thoracic radiotherapy<br>* 36 Gy to the primary lung tumor and present mediastinal node metastases after three months of medical treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in quality of life | LCSS, lung cancer symptom scale. A scale from zero to one-hundred, higher number indicate worse symptoms. | Three months after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | From randomization | 24 months | 
| Progression free survival | From randomization | 24 months | 
| Toxicity of esophagitis, pneumonitis, dyspnea, fatigue, cough | CTC (common toxicity criteria) version 4.0. Esophagitis, pneumonitis, dyspnea, fatigue, cough, worst grade. | During follow-up , up to 24 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, Radiotherapy, Quality of life