FLARE RT for Patients With Stage IIB-IIIB Non-small Cell Lung Cancer: Personalizing Radiation Therapy Using PET/CT and SPECT/CT Imaging

Study Overview
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Brief Summary
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This phase II trial studies how well positron emission tomography (PET)/computed tomography (CT) and single positron emission computed tomography (SPECT)/CT imaging works in improving radiation therapy treatment in patients with stage IIB-IIIB non-small cell lung cancer. PET/CT imaging mid-way through treatment may be able to accurately show how well radiation therapy and chemotherapy are working. SPECT/CT imaging may be able to tell which parts of the lung tissue are healthier than others. Based on the result of the imaging, treatment adjustments may be made to the radiation therapy to improve survival and decrease toxicity.

Detailed Description
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OUTLINE: This is a dose-escalation study of radiation therapy. Patients undergo functional avoidance radiation therapy during weeks 1-3. Patients undergo fludeoxyglucose F-18 FDG PET/CT at baseline, 3 weeks, and 3 months post-radiation therapy and undergo technetium Tc-99m albumin aggregated (99mTc-MAA) and technetium Tc-99m sulfur colloid SPECT/CT radiation therapy at baseline and 3 months post-radiation therapy. Baseline PET/CT must be performed at University of Washington Medical Center/Seattle Cancer Care Alliance and be within one month of treatment start, therefore some patients may need to repeat a baseline PET/CT if their PET/CT is from an outside institution or > 1 month old. Patients not responding to treatment at 3 weeks, will receive an increased daily radiation therapy dosage. After completion of study treatment, patients are followed up for 2 years.

Official Title
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Personalized Radiation Therapy Through Functional Lung Avoidance and Response-Adaptive Dose Escalation: Utilizing Multimodal Molecular Imaging to Improve the Therapeutic Ratio (FLARE RT)

Conditions
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Stage IIB Lung Non-Small Cell Carcinoma AJCC v7, Stage IIIA Lung Non-Small Cell Cancer AJCC v7, Stage IIIB Lung Non-Small Cell Cancer AJCC v7

Intervention / Treatment
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* Procedure: Computed Tomography
* Procedure: Computed Tomography
* Radiation: Fludeoxyglucose F-18
* Other: Laboratory Biomarker Analysis
* Procedure: Positron Emission Tomography
* Radiation: Radiation Therapy
* Procedure: Single Photon Emission Computed Tomography
* Radiation: Technetium Tc-99m Albumin Aggregated
* Radiation: Technetium Tc-99m Sulfur Colloid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically proven (either histologic or cytologic) diagnosis of stage IIB-IIIB non-small cell lung cancer (NSCLC); according to American Joint Committee on Cancer (AJCC) staging, 7th edition Staging workup must include: brain imaging (CT head or magnetic resonance imaging [MRI] brain) and PET/CT Pleural effusions must have cytology to rule out malignant involvement unless too small to undergo thoracentesis per radiology Patients must be considered unresectable or inoperable Patient must not have received prior radiation for this lung cancer Patients must be having concurrent chemotherapy Nodal recurrences can be treated on this protocol but prior curative surgery for lung cancer must have been at least 6 months prior to the nodal recurrence Patients must have measurable or evaluable disease that is FDG avid with standardized uptake value (SUV) > 3 on PET/CT Zubrod performance status 0-1 PFTs including forced expiratory volume in 1 second (FEV1) within 26 weeks prior to registration; for FEV1, the best value obtained pre- or post-bronchodilator must be >= 0.8 liters/second or >= 50% predicted Blood cell count (CBC)/differential obtained within 8 weeks prior to registration on study Absolute neutrophil count (ANC) >= 1,800 cells/mm^3 Platelets >= 100,000 cells/mm^3 Hemoglobin >= 10.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin (Hgb) >= 10.0 g/dl is acceptable) Serum creatinine within normal institutional limits or creatinine clearance >= 40 ml/min Bilirubin must be within or below normal institutional limits Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x the institutional upper limit of normal (IULN) Patient must sign study specific informed consent prior to study entry Exclusion Criteria: > 10% unintentional weight loss within the past month Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; non-invasive conditions such as carcinoma in situ of the breast, oral cavity, or cervix are all permissible Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception

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: Treatment<br>Patients undergo functional avoidance radiation therapy during weeks 1-3. Patients undergo fludeoxyglucose F-18 FDG PET/CT at baseline, 3 weeks, and 3 months post-radiation therapy and undergo technetium Tc-99m albumin aggregated (99mTc-MAA) and technetium Tc-99m sulfur colloid SPECT/CT radiation therapy at baseline and 3 months post-radiation therapy. Baseline PET/CT must be performed at University of Washington Medical Center/Seattle Cancer Care Alliance and be within one month of treatment start, therefore some patients may need to repeat a baseline PET/CT if their PET/CT is from an outside institution or > 1 month old. Patients not responding to treatment at 3 weeks, will receive an increased daily radiation therapy dosage. | Procedure: Computed Tomography<br>* Undergo FDG PET/CT<br>* Other names: tomography;Procedure: Computed Tomography<br>* Undergo Tc-99m MAA or Tc-99m DTPA<br>* Other names: tomography;Radiation: Fludeoxyglucose F-18<br>* Undergo FDG PET/CT<br>* Other names: Fluorodeoxyglucose F18;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Procedure: Positron Emission Tomography<br>* Undergo FDG PET/CT<br>* Other names: proton magnetic resonance spectroscopic imaging;Radiation: Radiation Therapy<br>* Undergo functional avoidance radiation therapy<br>* Other names: Therapy, Radiation;Procedure: Single Photon Emission Computed Tomography<br>* Undergo Tc-99m MAA or Tc-99m Undergo Tc-99m sulfur colloid SPECT/CT<br>* Other names: Tomography, Emission-Computed, Single-Photon;Radiation: Technetium Tc-99m Albumin Aggregated<br>* Undergo Tc-99m MAA SPECT/CT<br>* Other names: Technetium Tc 99m-Labeled Macroaggregated Albumin;Radiation: Technetium Tc-99m Sulfur Colloid<br>* Undergo Tc-99m sulfur colloid<br>* Other names: technetium Tc 99m sulfur colloid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) rate | Will be compared to the 60 Gy cohort of Radiation Therapy Oncology Group 0617 for historical control. A one sample proportionality test using all patients who complete either functional lung avoidance and response-adaptive dose escalation (FLARE) radiation therapy (RT) treatment arm (standard dose arm in responders + dose escalation arm in non-responders) will be performed. Interim and final statistical analyses of OS will consist of Kaplan-Meier estimation and cox proportional hazard regression. | At 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of pulmonary toxicity defined as Common Terminology Criteria for Adverse Events version 4 grade 2 or higher pneumonitis | Will be compared between patients receiving FLARE RT and historical rates. | Up to 3 months | 
| Local-regional control as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria | Intrathoracic control of lung tumors assessed by post-radiotherapy computed tomography. Control will be defined as lack of progressive disease as defined by RECIST criteria. Interim and final statistical analyses of local control will consist of Kaplan-Meier estimation and cox proportional hazard regression. | At 1 year | 
| Progression-free survival | Interim and final statistical analyses of local control will consist of Kaplan-Meier estimation and cox proportional hazard regression. | Up to 2 years | 
| Change in pulmonary function-forced expiratory volume in 1 second (FEV1) | Pulmonary function tests (FEV1, liters) will be performed and change over time will be evaluated. | Baseline to 3 months post-radiation therapy | 
| Change in pulmonary function (diffusing capacity of the lungs for carbon monoxide [DLCO]) | Pulmonary function tests (DLCO, % predicted) will be performed and change over time will be evaluated. | Baseline to 3 months post-radiation therapy |