Postoperative Radiotherapy of Non-small Cell Lung Cancer: Accelerated vs. Conventional Fractionation

Study Overview
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Brief Summary
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In this randomized multicentric phase II study it will be investigated whether an accelerated postoperative radiotherapy with photons or protons (7 fractions per week, 2 Gy single dose) may improve locoregional tumour control in non-small cell lung cancer (NSCLC) in comparison to conventional fractionation (5 fractions per week, 2 Gy single dose).

Detailed Description
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This study is a randomized multicentric trial. Within this study an accelerated irradiation schedule (7 fractions per week, 2 Gy single dose) will be compared with the currently used conventional fractionation schedule (5 fractions per week, 2 Gy single dose) for postoperative radiotherapy with photons or protons in patients with NSCLC. The primary endpoint is locoregional tumour control after 36 months. Secondary endpoints are overall survival of patients, local recurrence-free and distant metastases-free survival after 36 months, acute and late toxicity as well as quality of life for both treatment methods.

Official Title
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Postoperative Radiotherapy of Non-small Cell Lung Cancer: Accelerated vs. Conventional Fractionation

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Radiation: conventional fractionation
* Radiation: accelerated fraction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically confirmed non-small cell lung cancer previous tumor resection with curative intention postoperative indication for irradiation (> pN1 and/ or R1) R2-resection or recurrence postoperative/after adjuvant chemotherapy diagnosed by the restaging-imaging exclusion of distant metastases (M0) age > 18 years good general condition (ECOG performance status 0 or 1) written informed consent appropriate compliance to ensure close follow-up women of childbearing age: adequate contraception Exclusion Criteria: histologically confirmed small cell lung cancer distant metastases no written informed consent or lack of cooperation relating to therapy or follow-up previous (< 5 years) or concomitant other malignant disease (exception: malignant disease, which is very likely healed and not influenced therapy or follow up of the non-small cell lung cancer, e.g. carcinoma in-situ, basaliomas, very early skin cancers) for proton therapy: heart pacemaker previous radiotherapy of the thorax or lower neck region pregnancy or lactation participation in another intervention study or not completed follow-up of a intervention study. Exceptions are psychological studies, supportive or observation studies, the previous therapy of non-small cell lung cancer is in accordance with the guideline and the participation in radiotherapy studies is not excluded in the trial protocol of the previous study

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 |
| --- | --- |
| Active Comparator: conventional fractionation<br>radiotherapy with conventional fractionation (5 x 2Gy per week) | Radiation: conventional fractionation<br>* In this treatment arm patients will receive radiotherapy with the currently used conventional fractionation schedule i.e. 5 fractions per week, 2 Gy single dose.<br>|
| Active Comparator: accelerated fraction<br>radiotherapy with accelerated fraction (7 x 2 Gy per week) | Radiation: accelerated fraction<br>* In this treatment arm patients will receive radiotherapy with an accelerated fractionation schedule i.e. 7 fractions per week, 2 Gy single dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| assessment of local tumor control | Local tumor control will be assessed by appropriate non-invasive (CT or PET-CT) and if necessary invasive examination methods (bronchoscopy with biopsy). | 36 months after therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | Follow-up visits should be continued in all patients until death. Otherwise patients will be censored with date of the last follow-up. | 36 months after therapy | 
| local recurrence-free survival | Local-recurrences will be assessed by appropriate non-invasive (CT or PET-CT) and if necessary invasive examination methods (bronchoscopy with biopsy). | 36 months after therapy | 
| acute toxicity | The occurrence of acute side effects (up to 90 days after start of treatment) will be recorded and documented based on CTCAE 4.0. | Comparison after 20, 50, 100 and 200 patients have been treated. This number of patients is expected to be included after 6, 12, 18 and 40 months. | 
| quality of life | The assessment of quality of life is carried out using the established EORTC QLQ-C30 questionnaire and the additional lung module QLQ-LC13. Quality of life will be documented immediately before the start of therapy, after completion of postoperative radiotherapy and at every follow-up visit. | 36 months after therapy | 
| distant metastases-free survival | Distant metastases will be assessed by PET-CT or abdominal sonography and chest x-ray. | 36 months after therapy | 
| late toxicity | The occurrence of late side effects will be recorded and documented based on CTCAE 4.0 after every follow-up visit. | Comparison after 20, 50, 100 and 200 patients have been treated. This number of patients is expected to be included after 6, 12, 18 and 40 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-small cell lung cancer, radiotherapy, accelerated fractionation, conventional fractionation, postoperative