Stereotactic Body Radiotherapy Versus Conventional Radiotherapy in Medically-Inoperable Non-Small Lung Cancer Patients

Study Overview
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Brief Summary
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A multi-centre randomized controlled open-label trial in medically inoperable patients with biopsy-proven early stage non-small cell lung cancer (NSCLC). Eligible and consenting patients will be randomly allocated to receive stereotactic body radiotherapy (SBRT) or conventional radiotherapy (CRT) in a 2:1 ratio. Radiotherapy will be administered as soon as possible following randomization and subjects will be followed for 5 years post-randomization for cancer recurrence, toxicity and survival. The primary outcome is local control (LC). The trial will be conducted at 16-20 clinical centres throughout Canada.

Official Title
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A Randomized Trial of Medically-Inoperable Stage 1 Non-small Cell Lung Cancer Patients Comparing Stereotactic Body Radiotherapy Versus Conventional Radiotherapy

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Radiation: Stereotactic Body Radiotherapy (SBRT)
* Radiation: Conventional Radiotherapy (CRT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: T1/T2a N0 M0 NSCLC, either by: (a) histological confirmation (squamous cell, adenocarcinoma, large cell carcinoma, or not specified) and CT thorax and/or PET-CT evidence, or (b) a suspicious growing nodule on serial CT imaging, with malignant PET Fluorodeoxyglucose (FDG) avidity, for which a biopsy would be extremely risky. Deemed medically inoperable (as reviewed by a thoracic surgeon and defined as surgically resectable but, because of underlying physiological medical problems [e.g. chronic obstructive pulmonary disease (COPD), heart disease], surgery is contraindicated) or Radiotherapy is preferred by the patient due to high operable risk. Exclusion Criteria: Less than 18 years of age. Eastern Cooperative Oncology Group (ECOG) performance status 3 or higher. Prior invasive malignancy within the past 3 years (excluding non-melanomatous skin cancer). History of ataxia telangiectasia. Previous radiotherapy (RT) in the vicinity of the tumour, such that significant overlap could occur. Previous pneumonectomy with Stage I lung cancer in the remaining lung. Diagnosis of idiopathic pulmonary fibrosis and/or interstitial lung disease. Planned for other anticancer therapy (chemotherapy, biological targeted therapy). Female, who is currently pregnant or lactating. Geographic inaccessibility for follow-up. Unable to provide informed consent.

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stereotactic Body Radiotherapy<br>Stereotactic Body Radiotherapy (SBRT) | Radiation: Stereotactic Body Radiotherapy (SBRT)<br> <br> |
| Active Comparator: Conventional Radiotherapy<br>Conventional Radiotherapy (CRT) | Radiation: Conventional Radiotherapy (CRT)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Control | Local control is the absence of local recurrence during the study period. This is the time from randomization to primary tumour failure or marginal failure. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall Survival is defined as the time from randomization to death from any cause. Alive subjects will be censored on the date of last follow-up. | 5 years | 
| Disease-Free Survival | Disease-Free Survival is defined as the time from randomization to the earliest recurrence of disease or to death attributed to lung cancer. | 5 years | 
| Event-Free Survival | Event-Free Survival is defined as the time from randomization to the earliest documented recurrent disease or death from any cause. | 5 years | 
| Lung Cancer-Specific Survival | Lung Cancer-Specific Survival is defined as the time from randomization to death attributable to lung cancer | 5 years | 
| Radiation Treatment-Related Death | Radiation Treatment-Related Death is defined as death occurring between 1 to 12 months following treatment, and caused directly by radiation toxicity attributed to either catastrophic hemorrhage or to severe radiation pneumonitis leading to death | 1 to 12 months | 
| Toxicity | Acute Toxicity will be assessed at 3 months post-randomization and includes fatigue, dyspnea and esophagitis. Late toxicity will be assessed beyond 3 months and up to 5 years and includes radiation pneumonitis, chest wall pain and rib fracture. | 5 years | 
| Quality of Life | Impact on quality of life will be assessed with the European Organization for Research in Treatment of Cancer and the Lung Cancer-specific Module 13 questionnaires. | 2 years | 
| Cost-Utility | Cost-Utility will be assessed using the European Quality of Life questionnaire in conjunction with the overall survival results | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stereotactic body radiotherapy, conventional radiotherapy, inoperable patients, local control, cancer recurrence, toxicity, survival