Individualized Lung Tumor Stereotactic Ablative Radiotherapy (iSABR)

Study Overview
=================
Brief Summary
-----------------
A research study of a procedure to treating lung cancer with focused radiation called Stereotactic Ablative Radiotherapy (SABR). The purpose of this study is to evaluate the effectiveness of individualizing the dose of radiation used to treat lung tumors with SABR based on tumor-specific factors. While recent research has identified SABR as a promising method to increase local control (LC) of lung cancer, further research has indicated that tumor volume is a prognostic factor, with increased size/volume of tumor being associated with poorer outcomes. This study explores if a volume-adapted strategy for the radiologic exposure (dose) will improve efficacy in larger tumors (ie, > 10 cc). This is a study of the procedure stereotactic ablative radiotherapy (SABR). It is not a study of a specific drug or device.

Official Title
-----------------
Trial of Individualized Lung Tumor Stereotactic Ablative Radiotherapy (iSABR)

Conditions
-----------------
Non-small Cell Lung Cancer (NSCLC)

Intervention / Treatment
-----------------
* Radiation: iSABR, 25 Gray in 1 fraction for small peripheral tumors
* Radiation: iSABR, 50 Gray in 4 fractions for medium peripheral tumors
* Radiation: iSABR, 54 Gray in 3 fractions for large peripheral tumors
* Radiation: iSABR, 40 Gray in 4 fractions for small central tumors
* Radiation: iSABR, 50 Gray in 4 fractions for medium central tumors
* Radiation: iSABR, 60 Gray in 8 fractions for large central tumors


Participation Criteria
=================
Eligibility Criteria
-----------------
INCLUSION CRITERIA Limited primary non-small cell lung cancers (NSCLC) (ie, graded as T1aN0M0, T1bN0M0, T2aN0M0, T2bN0M0, or T3N0M0), or metastatic lung tumors with no evidence of uncontrolled extrathoracic metastases. Up to 4 lesions may be considered. For a single lesion, the sum of three orthogonal diameters can be no more than 20 cm. For multiple lesions, no lesion can have a sum of orthogonal diameters greater than 15 cm. Both peripheral and central tumors are accepted for this trial. Age ≥ 18 years old Patients may be enrolled more than once (eg, for a new tumor lesion) EXCLUSION CRITERIA Contraindication for radiotherapy Pregnant and breastfeeding women are excluded If prior radiation therapy, there is no overlap with the prior high dose regions (EXCEPTION: by approval of the investigators).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Health Services Research
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Limited Primary Non-small Cell Lung Cancer (NSCLC)<br>Participants with limited primary NSCLCs (graded as T1aN0M0, T1bN0M0, T2aN0M0, T2bN0M0, or T3N0M0) | Radiation: iSABR, 25 Gray in 1 fraction for small peripheral tumors<br>* Radiotherapy procedure for participants with small peripheral tumors ≤ 10 cc.<br>* Other names: Individualized Stereotactic Ablative Radiotherapy (iSABR);Radiation: iSABR, 50 Gray in 4 fractions for medium peripheral tumors<br>* Radiotherapy procedure for participants with medium peripheral tumors > 10 cc and ≤ 30 cc.<br>* Other names: Individualized Stereotactic Ablative Radiotherapy (iSABR);Radiation: iSABR, 54 Gray in 3 fractions for large peripheral tumors<br>* Radiotherapy procedure for participants with large peripheral tumors > 30 cc.<br>* Other names: Individualized Stereotactic Ablative Radiotherapy (iSABR);Radiation: iSABR, 40 Gray in 4 fractions for small central tumors<br>* Radiotherapy procedure for participants with small central tumors ≤ 10 cc.<br>* Other names: Individualized Stereotactic Ablative Radiotherapy (iSABR);Radiation: iSABR, 50 Gray in 4 fractions for medium central tumors<br>* Radiotherapy procedure for participants with medium central tumors > 10 cc and ≤ 30 cc.<br>* Other names: Individualized Stereotactic Ablative Radiotherapy (iSABR);Radiation: iSABR, 60 Gray in 8 fractions for large central tumors<br>* Radiotherapy procedure for participants with large central tumors > 30 cc.<br>* Other names: Individualized Stereotactic Ablative Radiotherapy (iSABR);|
| Experimental: History of NSCLC<br>Participants with prior history of NSCLC and new limited primary NSCLC lesion(s) | Radiation: iSABR, 25 Gray in 1 fraction for small peripheral tumors<br>* Radiotherapy procedure for participants with small peripheral tumors ≤ 10 cc.<br>* Other names: Individualized Stereotactic Ablative Radiotherapy (iSABR);Radiation: iSABR, 50 Gray in 4 fractions for medium peripheral tumors<br>* Radiotherapy procedure for participants with medium peripheral tumors > 10 cc and ≤ 30 cc.<br>* Other names: Individualized Stereotactic Ablative Radiotherapy (iSABR);Radiation: iSABR, 54 Gray in 3 fractions for large peripheral tumors<br>* Radiotherapy procedure for participants with large peripheral tumors > 30 cc.<br>* Other names: Individualized Stereotactic Ablative Radiotherapy (iSABR);Radiation: iSABR, 40 Gray in 4 fractions for small central tumors<br>* Radiotherapy procedure for participants with small central tumors ≤ 10 cc.<br>* Other names: Individualized Stereotactic Ablative Radiotherapy (iSABR);Radiation: iSABR, 50 Gray in 4 fractions for medium central tumors<br>* Radiotherapy procedure for participants with medium central tumors > 10 cc and ≤ 30 cc.<br>* Other names: Individualized Stereotactic Ablative Radiotherapy (iSABR);Radiation: iSABR, 60 Gray in 8 fractions for large central tumors<br>* Radiotherapy procedure for participants with large central tumors > 30 cc.<br>* Other names: Individualized Stereotactic Ablative Radiotherapy (iSABR);|
| Experimental: Advanced Lung Cancer Including Metastatic Lung Cancer<br>Participants with more advanced lung cancer or lung metastases from a variety of different cancers. | Radiation: iSABR, 25 Gray in 1 fraction for small peripheral tumors<br>* Radiotherapy procedure for participants with small peripheral tumors ≤ 10 cc.<br>* Other names: Individualized Stereotactic Ablative Radiotherapy (iSABR);Radiation: iSABR, 50 Gray in 4 fractions for medium peripheral tumors<br>* Radiotherapy procedure for participants with medium peripheral tumors > 10 cc and ≤ 30 cc.<br>* Other names: Individualized Stereotactic Ablative Radiotherapy (iSABR);Radiation: iSABR, 54 Gray in 3 fractions for large peripheral tumors<br>* Radiotherapy procedure for participants with large peripheral tumors > 30 cc.<br>* Other names: Individualized Stereotactic Ablative Radiotherapy (iSABR);Radiation: iSABR, 40 Gray in 4 fractions for small central tumors<br>* Radiotherapy procedure for participants with small central tumors ≤ 10 cc.<br>* Other names: Individualized Stereotactic Ablative Radiotherapy (iSABR);Radiation: iSABR, 50 Gray in 4 fractions for medium central tumors<br>* Radiotherapy procedure for participants with medium central tumors > 10 cc and ≤ 30 cc.<br>* Other names: Individualized Stereotactic Ablative Radiotherapy (iSABR);Radiation: iSABR, 60 Gray in 8 fractions for large central tumors<br>* Radiotherapy procedure for participants with large central tumors > 30 cc.<br>* Other names: Individualized Stereotactic Ablative Radiotherapy (iSABR);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate Local Tumor Control with Individually-optimized Stereotactic Ablative Radiotherapy (SABR) for lung tumors. | Tumor control will be assessed by CT, PET-CT, and if appropriate, biopsy. Tumor control is defined as a determination that the participant has not experienced Local Failure at the treatment lesion, meaning primary tumor failure or involved lobe failure or both. The outcome is reported as the number of participants who maintain tumor control for 1 year from the completion of Stereotactic Ablative Radiotherapy (SABR) treatment, a number without dispersion. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity of Individually-Optimized Stereotactic Ablative Radiotherapy (SABR) for Lung Tumors | In concept, toxicity refers to adverse events caused by an intervention, ie, related adverse events. Toxicity will be assessed on the basis of related pulmonary; esophageal; chest wall; skin; vascular; cardiac/pericardial; and neurologic adverse events. Such events may have a number of different preferred terms for the adverse effect. The outcome will be reported as the number of Grade 3 or higher adverse effect events (toxicities), by Common Terminology Criteria for Adverse Events (CTCAE) Body System. The following exceptions apply. Gastrointestinal Disorders, Grade 4-5 only Atelectasis (collapse of the lung or lobe), Grade 4-5 only Grade 3 Hypoxia, only if worse than baseline All deaths related to treatment will be included. The outcome is numbers without dispersion. | 1 year | 
| Feasibility of Using an Optimized Breath-hold Technique during Stereotactic Ablative Radiotherapy (SABR) to Treat Lung Tumors | Radiotherapeutic dose levels to the tumor lesion may be limited by the proximity of critical organs. Reduced dose levels is believed to be associated with reduced therapeutic effect. This study will assess an anatomically-optimized audio-visual biofeedback (AVB)-coached breath-hold technique assisted by fast radiotherapy delivery. Holding breath at a particular point in the breathing cycle may minimize proximity between tumor lesions and critical organs. In summary, participants will be coached to breath-hold at a certain point in their normal breathing cycle, and radiation will be quickly administered in bursts for several seconds. Up to 12 to 15 cycles of breath-hold may be needed to administer the desired dose level. Feasibility of this technique will be assessed as the number of patients able to reproduce the optimized breath-hold. The outcome is a number without dispersion. | up to 2 years | 
| Difference in Treatment Delivery Time Using an Optimized Breath-hold Technique | Radiotherapeutic dose levels to the tumor lesion may be limited by the proximity of critical organs. Reduced dose levels is believed to be associated with reduced therapeutic effect. This study will assess an anatomically-optimized audio-visual biofeedback (AVB)-coached breath-hold technique assisted by fast radiotherapy delivery. Holding breath at a particular point in the breathing cycle may minimize proximity between tumor lesions and critical organs. In summary, participants will be coached to breath-hold at a certain point in their normal breathing cycle, and radiation will be quickly administered in bursts for several seconds. Up to 12 to 15 cycles of breath-hold may be needed to administer the desired dose level. Utility of this technique will be assessed as the difference in treatment delivery time compared to free-breathing treatment, reported as the median with standard deviation. | up to 2 years | 
| Progression-free survival (PFS) | Progression-free survival (PFS) is a measure of participant survival without disease recurrence, relapse, metastasis, or progression. The outcome is reported as the number of participants who were alive 2 years after the completion of Stereotactic Ablative Radiotherapy (SABR) treatment, and without disease progression during that time. The outcome is a number without dispersion. | up to 2 years | 
| Metastasis-free Survival (MFS) | Metastasis refers to the ability of cancer cells to break free of a tumor, and migrate to another location in the body and start a new tumor lesion. Metastasis-free survival (MFS) is a measure of participant survival without disease metastasis. The outcome is reported as the number of participants who were alive 2 years after the completion of Stereotactic Ablative Radiotherapy (SABR) treatment, and without documented metastasis in that time. The outcome is a number without dispersion. | 2 years | 
| Overall Survival (OS) | Overall survival (OS) is a measure of participant survival without regard to disease status. The outcome is reported as the number of participants who were documented as alive 2 years after the completion of Stereotactic Ablative Radiotherapy (SABR) treatment. The outcome is a number without dispersion. | 2 years |