Study of LUNG Stereotactic Adaptive Ablative Radiotherapy

Study Overview
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Brief Summary
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The proposed study expands on the principles of SBRT (Stereotactic Body Radiation Therapy) and SABR (Stereotactic Ablative Radiotherapy) for centrally located NSCLC (Non-Small Cell Lung Cancer) to further optimize outcomes in this patient population with utilization of the adaptive workflow to maintain tumor control rates but decrease the incidence and grade of treatment-related toxicities.

Official Title
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Phase II Study of LUNG Stereotactic Adaptive Ablative Radiotherapy for Central and Ultracentral Tumors

Conditions
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Lung Cancer, Lung Tumor

Intervention / Treatment
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* Radiation: Stereotactic Adaptive Ablative Radiotherapy at 50 Gy (Gray)
* Radiation: Stereotactic Adaptive Ablative Radiotherapy at 60 Gy (Gray)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years of age Clinical diagnosis of NSCLC Stage T1-2b (≤ 5 cm) Exclusion Criteria: Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1 year (i.e., carcinomas in situ of the breast, oral cavity, or cervix are permissible); previous lung cancer, if the patient is disease-free for a minimum of 1 year is permitted; Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields Prior chemotherapy for the study cancer Plans for the patient to receive other local therapy (including standard fractionated radiotherapy and/or surgery) while on this study, except at disease progression Plans for the patient to receive systemic therapy (including standard chemotherapy or biologic targeted agents), while on this study, except at disease progression

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: Central lung tumors<br>Gross tumor volume (GTV) less than or equal to 1 cm from a lobar bronchus | Radiation: Stereotactic Adaptive Ablative Radiotherapy at 50 Gy (Gray)<br>* Cohort A will include 30 patients with central tumors; the dose regimen prescribed is 50 Gy (Gray) in 5 fractions with a 40 hour inter-fraction interval.<br>|
| Experimental: Cohort B: Ultra-central lung tumors<br>Gross tumor volume (GTV) less than or equal to 1 cm from the mainstem bronchus, trachea, or esophagus | Radiation: Stereotactic Adaptive Ablative Radiotherapy at 60 Gy (Gray)<br>* Cohort B will include 30 patients with ultra-central tumors; the dose regimen prescribed is 60 Gy (Gray) in 8 fractions on consecutive days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment completion | Number of patients who completed treatment within +/- 5 days of intended treatment. | Plus or minus 5 days of treatment | 
| Number of patients experiencing adverse events | No greater than 15 percent of patients experience a 12-month ≥ grade 3 toxicity and ≤1 grade 5 toxicity possibly, probably, or definitely related to treatment. | 12-month of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Tumor Control Rate | Primary tumor control rate at the maximum tolerated dose (MTD) based on each treatment cohort. | 1 year of treatment | 
| Progression-free survival (PFS) | Progression-free survival (PFS) is defined as the first occurrence of local and/or regional disease progression, distant metastases, second primary tumor, or death due to any cause. PFS time is measured from the date of start of SBRT to the date of the failure event for PFS. | 1 year of treatment | 
| Overall survival (OS) | Overall survival (OS) time is measured from the date of start of SBRT to the date of death due to any cause. | 1 year of treatment | 
| Functional Assessment of Cancer Therapy - Lung (FACT-L) | The Functional Assessment of Cancer Therapy - Lung (FACT-L) quality of life instrument has been extensively used for measuring quality of life in patients with lung cancer. There are 5 sections dealing with physical, family, emotional, functional well-being, and additional concerns. There are nine questions that are specific to lung cancer (LSC), including shortness of breath, cough, etc. The TOI (Trial Outcome Index) is the sum of the scores on the LCS and the physical well-being and functional well-being subscales of the FACT-L scale. | Baseline | 
| EQ-5D-5L | The five-item index score from EQ-5D-5L will be used to generate utility scores that will lie between 0 (Worst health state) and 1 (Best health state). | 3 and 12-month follow-up | 
| Late-Toxicity | Rate of late (>1 year) ≥ grade 3 adverse events related to treatment | 1 year of treatment |