Study of Hypofractionated Radiotherapy Alone in Locally Advanced Nonsmall Cell Lung Cancer Patients

Study Overview
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Brief Summary
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The purpose of this research study is to find out what effects (good or bad) may come from a new way of doing radiation therapy for lung cancer. This study is for patients who are not able to get surgery or chemotherapy with their radiation. The way of doing radiation therapy in this trial is called hypofractionated radiation therapy which is a standard approach, but this study allows the actual tumor to get an extra radiation dose while still protecting the organs that are near the tumor.

Detailed Description
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Primary Objective: • To determine the in-field control of hypofractionated radiotherapy consisting of 70 Gy in 25 fractions without concurrent chemotherapy measured at two years after the first post- radiotherapy scan. Secondary Objective(s): To determine the toxicity profile of thoracic hypofractionated radiotherapy consisting of 70 Gy in 25 fractions as graded by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 To determine proportion with local, regional, and distant progression at 1 and 2 years after the first post-radiotherapy scan, and compute progression-free and overall survival (progression-free survival and overall survival, respectively).

Official Title
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A Single Arm Phase II Study of Hypofractionated Radiotherapy Alone in Locally Advanced Nonsmall Cell Lung Cancer Patients Who Decline or Are Ineligible for Surgery or Chemotherapy

Conditions
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Nonsmall Cell Lung Cancer, Stage II, Nonsmall Cell Lung Cancer Stage III

Intervention / Treatment
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* Drug: Hypofractionated Radiation Therapy
* Radiation: Radiation Boost


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological confirmation of non-small cell lung cancer by either biopsy or cytology American Joint Committee on Cancer (AJCC) 8th Edition Stage II-III or ultracentral Stage IB disease as determined by PET/CT and MRI Brain Ultracentral disease will be defined as edge of gross visible tumor within 1.0 cm of the proximal bronchial tree. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-3 Participant is not eligible for or has declined surgical resection or stereotactic body radiotherapy as determined by the treating physician Participant is not eligible for or has declined concurrent chemotherapy as determined by the treating physician While investigators expect it to be an uncommon event, sequential use of systemic therapy after completion of radiation therapy is permissible if the participant's status improves such that they become eligible for such therapies, per the discretion of a multidisciplinary tumor board. Negative serum or urine pregnancy test within 2 weeks of the date of enrollment for women of child-bearing potential. Ability to understand and the willingness to sign an IRB-approved informed consent document (either directly or via a legally authorized representative). Exclusion Criteria: History of previous thoracic radiotherapy with the exception of prior radiotherapy for breast cancer without overlap of the fields with the cancer to be treated. Prior systemic therapy or surgery for the study cancer. Prior malignancy within the past two years except for non-melanoma skin cancer, prostate cancer, or any in-situ malignancy. Receipt of anti-angiogenic therapy, such as bevacizumab, within 6 months of enrollment. Pregnant women are excluded from this study because radiation therapy has known potential for teratogenic or abortifacient effects.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypofractionated Radiation Therapy<br>Hypofractionated radiation therapy will be delivered to all participants. The radiation will be planned in a special way to give the biggest parts of the tumors that are the most difficult to control a little more radiation every day than the lower risk areas. | Drug: Hypofractionated Radiation Therapy<br>* The prescribed dose will be 70 Gy in 25 fractions. Participants will radiation therapy once a day for 25 days, Monday through Friday (around 5 weeks).<br>Radiation: Radiation Boost<br>* Undergo simultaneous integrated boost (SIB) to treat both planned target volumes with daily image guidance. This approach allows daily confirmation of target localization and simultaneous delivery of lower dose per fraction to low risk areas while maintaining a high dose per fraction to the highest risk areas.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence or Absence of In-Field Progression | In-field progression is defined as growth of the targeted lesions beyond the treated volume. The treated volume will be defined as the 28.75 Gy isodose line (50% of 57.5 Gy). Pathologic confirmation of tumor progression is preferred, but can be determined radiographically by Multidisciplinary Thoracic Oncology Program consensus if biopsy of the lesion in question is not feasible or safe. Investigators will compare the proportion of the sample with any in-field progression at 2 years to the historical control proportion of 0.5, using a one-sample z-test. | At 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants Experiencing Grade 2 or Higher Toxicities | Toxicities will be evaluated per Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 constructed with a 95% confidence interval. | 25 months | 
| Proportion of Participants That Experienced Local Progression | Participants who have experienced local progression by 13 months (1 year following first post-radiotherapy scan) and by 25 months (2 years following first post-radiotherapy scan), and will also compute the same two proportions considering regional progression, distant progression, and any (of the 3 categories) progression. A 95% confidence intervals around these proportions will be constructed. Participants for whom investigators are unable to determine progression status at 1 and 2 years (e.g., because they do not return for the necessary scans, or because they die without evidence of progression) will be left out of these analyses. | At 1 and 2 years after first post-radiotherapy scan | 
| Progression-Free Survival | Progression-free survival will be evaluated by considering the time from registration to progression of disease or death; those who do not experience either outcome will be censored at date of last visit. Using the Kaplan-Meier lifetable method, and will estimate median survival and corresponding 95% confidence intervals; investigators will also explore simple Cox proportional hazards models of this survival outcomes, to examine the predictive influence of variables such as age, gender, ECOG performance status, stage at diagnosis, planning target volume (PTV) 7000 volume, and planning target volume (PTV) 5750 volume. | Up to 2 years | 
| Overall Survival | Overall survival will be evaluated by considering the time from registration to death from any cause; those who do not die will be censored at date of last visit. Using the Kaplan-Meier lifetable method, and will estimate median survival and corresponding 95% confidence intervals; investigators will also explore simple Cox proportional hazards models of this survival outcomes, to examine the predictive influence of variables such as age, gender, ECOG performance status, stage at diagnosis, planning target volume (PTV) 7000 volume, and planning target volume (PTV) 5750 volume. | Up to 2 years |