Dose-Deescalated 3-Fraction Stereotactic Body Radiotherapy For Centrally Located Lung Cancer

Study Overview
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Brief Summary
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The purpose of this trial is to test a deescalated 3-fraction stereotactic body radiotherapy (SBRT) regimen to 45 Gray (Gy) in 3 fractions for centrally located thoracic tumors.

Detailed Description
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The purpose of this trial is to test a deescalated 3-fraction SBRT regimen to 45 Gy in 3 fractions for centrally located thoracic tumors in a phase II trial. This will provide prospectively collected data on the safety and efficacy of a three-fraction regimen in the previously defined No Fly Zone for both primary non-small cell lung cancer (NSCLC) and for lung metastases of any histology. This registration describes the design and eligibility criteria for the 36 NSCLC subjects the investigators plan to enroll. Local control, cancer-specific survival, and overall survival results from the NSCLC patients will be compared to both 3- and 5-fraction historical controls, specifically RTOG 0236 and 0813 results. The outcomes of the metastatic patients will also be reported. There will also be a quality-of-life component to the study to assess the impact of a shorter overall treatment time and the clinical impact of radiation side effects.

Official Title
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Phase IB/II Trial Of Dose-Deescalated 3-Fraction Stereotactic Body Radiotherapy For Centrally Located Lung Cancer

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Radiation: 45 Gray (Gy) regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Lung tumors will be ≤ 5 cm and centrally located, meaning any portion of gross tumor volume located within 2 cm of (but not abutting) the proximal bronchial tree (trachea, carina, right and left main bronchi, right and left upper lobe bronchi, bronchus intermedius, right middle lobe bronchus, lingular bronchus, right and left lower lobe bronchi), or within 2 cm of (whether abutting or not) major vessels, esophagus, or heart (based on RTOG and MD Anderson Cancer Center definitions 33,34). Multiple concurrent isocenters are allowed if at least one tumor meets the above criteria, and if all dose constraints for the plan summation can be met. These concurrent tumors other than study target lesion can be treated as per SOC and does not necessarily have to meet the above size limit. The PI will review and prospectively approve any lesions abutting these organs ECOG Performance Status of 0-2 Age > 18 Patients must sign a study-specific consent form. Exclusion Criteria: prior history of radiotherapy near target lesion resulting in overlapping treatment fields. Previously irradiated will be defined as organ at risk (OAR) structures in the receiving the following doses ( in <3 Gray (Gy) per fraction): Spinal cord previously irradiated to > 40 Gy, Brachial plexus previously irradiated to > 50 Gy, Small intestine, large intestine, or stomach previously irradiated to > 45 Gy, Brainstem previously irradiated to > 50 Gy, Lung previously irradiated with prior V20Gy > 35%. No active systemic, pulmonary, or pericardial infection No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung No significant cardiac disease, including the following: unstable angina, New York Heart Association class II-IV congestive heart failure, myocardial infarction within six months prior to study enrollment May not be pregnant or lactating No other medical condition or reason that, in the opinion of the investigator, would preclude study participation

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
Interventional Model Description: The intervention group will be compared with historical controls.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 45 Gy<br>Deescalated 3-fraction stereotactic body radiotherapy regimen to 45 Gy in 3 fractions. | Radiation: 45 Gray (Gy) regimen<br>* Deescalated 3-fraction stereotactic body radiotherapy regimen to 45 Gy in 3 fractions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of the stereotactic body radiotherapy regimen (SBRT) | Safety will be assessed by acute (defined as within 90 days of stereotactic body radiotherapy (SBRT)) and late (from 91 days through 2 years post-SBRT) toxicities. Toxicities are based on (Common Terminology Criteria for adverse events) CTCAE v. 5 criteria | From administration of SBRT up to 2 years post-SBRT | 
| local control (LC) of 3-fraction stereotactic body radiotherapy | The absence of primary tumor failure. Primary tumor failure is defined as Increase in tumor dimension of 20%. | Up to 10 years post-enrollment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| lobar control | Absence of primary tumor failure or involved lobe failure or both. | Up to 10 years post-enrollment. | 
| regional control | Absence of measurable tumor within lymph nodes along the natural lymphatic drainage typical for the location of the treated primary disease only with dimension of at least 1.0 cm on imaging studies (preferably computer tomography scans) within the lung, bronchial hilum, or the mediastinum. | Up to 10 years post-enrollment. | 
| distant control |  | Up to 10 years post-enrollment. | 
| overall survival |  | Up to 10 years post-enrollment. | 
| progression-free survival |  | Up to 10 years post-enrollment. |