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

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

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.

Study Overview

• Status: Completed
• Conditions: 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: Other: Laboratory Biomarker Analysis; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Radiation: Fludeoxyglucose F-18; Procedure: Computed Tomography; Radiation: Radiation Therapy; Procedure: Single Photon Emission Computed Tomography; Radiation: Technetium Tc-99m Albumin Aggregated; Radiation: Technetium Tc-99m Sulfur Colloid

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium
    • Seattle, Washington, United States, 98133
      • SCCA Proton Therapy Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment; 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.

Other: Laboratory Biomarker Analysis; Correlative studies; Procedure: Computed Tomography; Undergo FDG PET/CT; Other Names: CT; CAT; CAT Scan; Computerized Axial Tomography; tomography; computerized tomography; CT SCAN; Procedure: Positron Emission Tomography; Undergo FDG PET/CT; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; Radiation: Fludeoxyglucose F-18; Undergo FDG PET/CT; Other Names: 18FDG; FDG; fludeoxyglucose F 18; Fludeoxyglucose F18; Fluorine-18 2-Fluoro-2-deoxy-D-Glucose; Fluorodeoxyglucose F18; Procedure: Computed Tomography; Undergo Tc-99m MAA or Tc-99m DTPA; Other Names: CT; CAT; CAT Scan; Computerized Axial Tomography; tomography; computerized tomography; CT SCAN; Radiation: Radiation Therapy; Undergo functional avoidance radiation therapy; Other Names: Cancer Radiotherapy; Irradiate; Irradiated; Radiotherapeutics; RT; Therapy, Radiation; irradiation; radiotherapy; RADIATION; Procedure: Single Photon Emission Computed Tomography; Undergo Tc-99m MAA or Tc-99m Undergo Tc-99m sulfur colloid SPECT/CT; Other Names: Medical Imaging, Single Photon Emission Computed Tomography; Single Photon Emission Tomography; single-photon emission computed tomography; SPECT; SPECT imaging; SPECT SCAN; SPET; tomography, emission computed, single photon; Tomography, Emission-Computed, Single-Photon; Radiation: Technetium Tc-99m Albumin Aggregated; Undergo Tc-99m MAA SPECT/CT; Other Names: Tc 99m-labeled MAA; Technetium Tc 99m-Labeled Macroaggregated Albumin; Radiation: Technetium Tc-99m Sulfur Colloid; Undergo Tc-99m sulfur colloid; Other Names: Tc-99m SC; Tc 99m sulfur colloid; technetium Tc 99m sulfur colloid

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jing Zeng, Fred Hutch/University of Washington Cancer Consortium

Publications and helpful links

General Publications

• Horn KP, Thomas HMT, Vesselle HJ, Kinahan PE, Miyaoka RS, Rengan R, Zeng J, Bowen SR. Reliability of Quantitative 18F-FDG PET/CT Imaging Biomarkers for Classifying Early Response to Chemoradiotherapy in Patients With Locally Advanced Non-Small Cell Lung Cancer. Clin Nucl Med. 2021 Nov 1;46(11):861-871. doi: 10.1097/RLU.0000000000003774.
• Duan C, Chaovalitwongse WA, Bai F, Hippe DS, Wang S, Thammasorn P, Pierce LA, Liu X, You J, Miyaoka RS, Vesselle HJ, Kinahan PE, Rengan R, Zeng J, Bowen SR. Sensitivity analysis of FDG PET tumor voxel cluster radiomics and dosimetry for predicting mid-chemoradiation regional response of locally advanced lung cancer. Phys Med Biol. 2020 Oct 7;65(20):205007. doi: 10.1088/1361-6560/abb0c7.
• Bowen SR, Hippe DS, Chaovalitwongse WA, Duan C, Thammasorn P, Liu X, Miyaoka RS, Vesselle HJ, Kinahan PE, Rengan R, Zeng J. Voxel Forecast for Precision Oncology: Predicting Spatially Variant and Multiscale Cancer Therapy Response on Longitudinal Quantitative Molecular Imaging. Clin Cancer Res. 2019 Aug 15;25(16):5027-5037. doi: 10.1158/1078-0432.CCR-18-3908. Epub 2019 May 29.

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2016
• Primary Completion (Actual): June 1, 2023
• Study Completion (Actual): December 1, 2023

Study Registration Dates

• First Submitted: April 28, 2016
• First Submitted That Met QC Criteria: May 11, 2016
• First Posted (Estimated): May 16, 2016

Study Record Updates

• Last Update Posted (Actual): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 15, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Radiopharmaceuticals; Fluorodeoxyglucose F18; Deoxyglucose; Technetium Tc 99m Aggregated Albumin; Technetium Tc 99m Sulfur Colloid
• Other Study ID Numbers: 9599 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium); NCI-2016-00543 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); R01CA204301 (U.S. NIH Grant/Contract); RG3116002 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO