Clinical trial NCT02773238: FLARE RT for Patients With Stage IIB-IIIB Non-small Cell Lung Cancer: Personalizing Radiation Therapy Using PET/CT and SPECT/CT Imaging
Official title: Personalized Radiation Therapy Through Functional Lung Avoidance and Response-Adaptive Dose Escalation: Utilizing Multimodal Molecular Imaging to Improve the Therapeutic Ratio (FLARE RT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2016-05-16
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival (OS) Rate
timeFrame: At 2 years
Secondary outcomes:
measure: Radiation Pneumonitis Defined as Common Terminology Criteria for Adverse Events Version 4 Grade 2 or Higher Pneumonitis
timeFrame: Up to 3 months
measure: Local-Regional Progression as Defined by Response Evaluation Criteria In Solid Tumors (RECIST) Criteria
timeFrame: At 1 year
measure: Progression-free Survival (PFS)
timeFrame: 1 year
measure: Change in Pulmonary Function-forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline to 3 months post-radiation therapy
measure: Change in Pulmonary Function (Diffusing Capacity of the Lungs for Carbon Monoxide [DLCO])
timeFrame: Baseline to 3 months post-radiation therapy
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
city: Seattle
country: United States
facility: SCCA Proton Therapy Center
state: Washington
Study officials:
affiliation: Fred Hutch/University of Washington Cancer Consortium
name: Jing Zeng
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.