A Randomized Phase III Study of Palliative Radiation of Advanced Central Tumors With Intentional Avoidance of the Esophagus

Study Overview
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Brief Summary
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A randomized phase II study of palliative radiation of advanced central lung tumors with intentional avoidance of the esophagus. Patients will be randomized between standard of care palliative thoracic radiation and esophageal-sparing intensity-modulated radiation therapy (ES-IMRT) in a 1:1 ratio. Radiotherapy will be administered as soon as possible following randomization and subjects will be followed for 1 year after completion of their radiation therapy. The primary endpoint is esophageal quality of life as measured by the Esophageal Cancer Subscore (ECS) of the Functional Assessment of Cancer Therapy-Esophagus (FACT-E).

Official Title
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A Randomized Phase III Study of Palliative Radiation of Advanced Central Tumors With Intentional Avoidance of the Esophagus

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Radiation: Conventional radiotherapy
* Radiation: Esophageal-Sparing Intensity-Modulated Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: American Joint Committee on Cancer (AJCC) 7th edition stage IV NSCLC or stage III not eligible for curative intent treatment Intended to receive palliative radiotherapy to the thorax, to a dose of 30Gy in 10 fractions or 20Gy in 5 fractions. In either treatment arm at least 5cm of the esophagus should be in the intended treatment field. Willingness and ability to provide informed consent Eastern Cooperative Oncology Group (ECOG) performance status 0-3 Age 18 years or older Prior or planned systemic therapy (chemotherapy, immunotherapy, targeted agents) is permissible at the discretion of the treating medical oncologist, provided that no systemic treatment is given within 2 weeks prior to RT, concurrent with RT or within a 2-week period post RT. Concurrent palliative RT to other metastatic sites is permissible Life expectancy > 3 months Exclusion Criteria: Prior thoracic RT Serious medical comorbidities precluding RT Pregnant or lactating women Inability to attend the full course of RT or planned follow-up visits Planned concurrent palliative RT to the stomach and/or liver Congenital abnormalities of the esophagus or severe disorders of the esophagus (e.g. achalasia)

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Palliative Radiation<br>Patients in the standard arm will receive a conventional radiotherapy dose will be either 30 gray (Gy) in 10 fraction or 20Gy in 5 fractions. Patients will be stratified by intended dose prior to randomization. Radiation for patients in the standard arm should adhere to the principles of palliative radiation, with goals of alleviating symptoms or preventing potential complications. | Radiation: Conventional radiotherapy<br>* Patients will receive standard palliative radiation in dose of 30Gy in 10 fractions, or 20Gy in 5 fractions.<br>|
| Experimental: Esophageal Sparing IMRT<br>Patients on the experimental arm will receive esophageal-sparing intensity-modulated radiotherapy, with the same dose(s) as in the standard arm. | Radiation: Esophageal-Sparing Intensity-Modulated Radiotherapy<br>* Patients will receive esophageal-sparing intensity-modulated radiotherapy, of 30Gy in 10 fractions or 20Gy in 5 fractions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Esophageal Quality of Life | Esophageal quality of life will be measured by the ECS of the FACT-E, measured at 2 weeks. | 2 weeks after completion of radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | Survival | 6 months after completion of radiotherapy | 
| Toxicity Rate Differences | Differences in rates of grade 2 or higher toxicity between groups will be tested using the Fisher's Exact test. | 6 months after completion of radiotherapy | 
| Progression-Free Survival | Differences in local/regional progression-free survival will be tested using the stratified log-rank test | 6 months after completion of radiotherapy | 
| Further Systemic Therapy | Differences in number of cycles of further systemic therapy will be tested using the student's t-test | 6 months after completion of radiotherapy | 
| Cost-Effectiveness/Utility Analysis | European Quality of Life-5 Dimensions (EQ-5D) measurements will be converted into utilities to inform cost-effectiveness/utility analysis. | 6 months after completion of radiotherapy | 
| Dosimetry Comparison - Gross Tumor Volume (GTV) | Dosimetric comparison of GTV will be compared using the student's t-test. | 6 months after completion of radiotherapy | 
| Dosimetry Comparison - Planning Target Volume (PTV) | Dosimetric comparison of PTV will be compared using the student's t-test. | 6 months after completion of radiotherapy | 
| Dosimetry Comparison - Pulmonary Metrics | Dosimetric comparison of standard pulmonary metrics will be compared using the student's t-test. | 6 months after completion of radiotherapy | 
| Dosimetry Comparison - Esophageal Metrics | Dosimetric comparison of standard esophageal metrics will be compared using the student's t-test. | 6 months after completion of radiotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Esophageal sparing, Conventional radiotherapy, Palliative radiation, Central lung tumors