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

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

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.

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Interventions

PROCEDUREComputed Tomography

Undergo FDG PET/CT

RADIATIONFludeoxyglucose F-18

Undergo FDG PET/CT

OTHERLaboratory Biomarker Analysis

Correlative studies

PROCEDUREPositron Emission Tomography

Undergo FDG PET/CT

RADIATIONRadiation Therapy

Undergo functional avoidance radiation therapy

PROCEDURESingle Photon Emission Computed Tomography

Undergo Tc-99m MAA or Tc-99m Undergo Tc-99m sulfur colloid SPECT/CT

RADIATIONTechnetium Tc-99m Albumin Aggregated

Undergo Tc-99m MAA SPECT/CT

RADIATIONTechnetium Tc-99m Sulfur Colloid

Undergo Tc-99m sulfur colloid

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame	Description
Overall Survival (OS) Rate	At 2 years	Final statistical analyses of OS will consist of Kaplan-Meier estimation.

Secondary

Measure	Time frame	Description
Radiation Pneumonitis Defined as Common Terminology Criteria for Adverse Events Version 4 Grade 2 or Higher Pneumonitis	Up to 3 months	Common Terminology Criteria for Adverse Events version 4, grade 2 or higher pneumonitis is defined as breathing problems after radiation treatment requiring medications for treatment (grade 2), oxygen use (grade 3), hospitalization (grade 4), or leading to death (grade 5). Clinical studies commonly report how many patients that develop pneumonitis as a result of radiation treatment, which is usually within the first 3 months after radiation.
Local-Regional Progression as Defined by Response Evaluation Criteria In Solid Tumors (RECIST) Criteria	At 1 year	Intrathoracic progression of lung tumors assessed by post-radiotherapy computed tomography. Progression will be defined by RECIST criteria. Final statistical analyses of local-regional progression cumulative incidence will consist of Fine-Gray estimation with death and distant metastasis as competing risks.
Progression-free Survival (PFS)	1 year	Progression-free survival will be assessed by post-radiotherapy computed tomography. Progression will be defined by RECIST criteria. Final statistical analyses of PFS will consist of Kaplan-Meier estimation.
Change in Pulmonary Function-forced Expiratory Volume in 1 Second (FEV1)	Baseline to 3 months post-radiation therapy	Pulmonary function tests (FEV1, liters) will be performed and change over time will be evaluated.
Change in Pulmonary Function (Diffusing Capacity of the Lungs for Carbon Monoxide [DLCO])	Baseline to 3 months post-radiation therapy	Pulmonary function tests (DLCO, % predicted) will be performed and change over time will be evaluated.

Countries

United States

Participant flow

Participants by arm

Arm	Count
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. Computed Tomography: Undergo FDG PET/CT Computed Tomography: Undergo Tc-99m MAA or Tc-99m DTPA Fludeoxyglucose F-18: Undergo FDG PET/CT Laboratory Biomarker Analysis: Correlative studies Positron Emission Tomography: Undergo FDG PET/CT Radiation Therapy: Undergo functional avoidance radiation therapy Single Photon Emission Computed Tomography: Undergo Tc-99m MAA or Tc-99m Undergo Tc-99m sulfur colloid SPECT/CT Technetium Tc-99m Albumin Aggregated: Undergo Tc-99m MAA SPECT/CT Technetium Tc-99m Sulfur Colloid: Undergo Tc-99m sulfur colloid	51
Total	51

Arm

Count

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. Computed Tomography: Undergo FDG PET/CT Computed Tomography: Undergo Tc-99m MAA or Tc-99m DTPA Fludeoxyglucose F-18: Undergo FDG PET/CT Laboratory Biomarker Analysis: Correlative studies Positron Emission Tomography: Undergo FDG PET/CT Radiation Therapy: Undergo functional avoidance radiation therapy Single Photon Emission Computed Tomography: Undergo Tc-99m MAA or Tc-99m Undergo Tc-99m sulfur colloid SPECT/CT Technetium Tc-99m Albumin Aggregated: Undergo Tc-99m MAA SPECT/CT Technetium Tc-99m Sulfur Colloid: Undergo Tc-99m sulfur colloid

51

Total

51

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Lack of Efficacy	4

Baseline characteristics

Characteristic	Treatment
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	21 Participants
Age, Categorical Between 18 and 65 years	30 Participants
Age, Continuous	63.2 years STANDARD_DEVIATION 8.1
Race (NIH/OMB) American Indian or Alaska Native	3 Participants
Race (NIH/OMB) Asian	6 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants
Race (NIH/OMB) White	36 Participants
Region of Enrollment United States	51 Participants
Sex: Female, Male Female	28 Participants
Sex: Female, Male Male	23 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	24 / 51
other Total, other adverse events	49 / 51
serious Total, serious adverse events	6 / 51

Outcome results

Primary

Overall Survival (OS) Rate

Final statistical analyses of OS will consist of Kaplan-Meier estimation.

Time frame: At 2 years

Arm	Measure	Value (NUMBER)
Treatment	Overall Survival (OS) Rate	54.2 percentage of patients

Secondary

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.

Time frame: Baseline to 3 months post-radiation therapy

Population: Only 45 patients went through both baseline and 3-months post-radiation testing.

Arm	Measure	Value (MEAN)	Dispersion
Treatment	Change in Pulmonary Function (Diffusing Capacity of the Lungs for Carbon Monoxide [DLCO])	-8 percentage of predicted lung function	Standard Deviation 5.2

Secondary

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.

Time frame: Baseline to 3 months post-radiation therapy

Population: 51 patient had pre-radiation PFTs done, but only 45 patients had 3-months post-radiation PFTs performed. Patients either withdrew from study due to cancer progression or declined the repeat testing.

Arm	Measure	Value (MEAN)	Dispersion
Treatment	Change in Pulmonary Function-forced Expiratory Volume in 1 Second (FEV1)	-0.15 liters	Standard Deviation 0.09

Secondary

Local-Regional Progression as Defined by Response Evaluation Criteria In Solid Tumors (RECIST) Criteria

Intrathoracic progression of lung tumors assessed by post-radiotherapy computed tomography. Progression will be defined by RECIST criteria. Final statistical analyses of local-regional progression cumulative incidence will consist of Fine-Gray estimation with death and distant metastasis as competing risks.

Time frame: At 1 year

Arm	Measure	Value (NUMBER)
Treatment	Local-Regional Progression as Defined by Response Evaluation Criteria In Solid Tumors (RECIST) Criteria	12.2 percentage of patients

Secondary

Progression-free Survival (PFS)

Progression-free survival will be assessed by post-radiotherapy computed tomography. Progression will be defined by RECIST criteria. Final statistical analyses of PFS will consist of Kaplan-Meier estimation.

Time frame: 1 year

Arm	Measure	Value (NUMBER)
Treatment	Progression-free Survival (PFS)	53.1 percentage of patients

Secondary

Radiation Pneumonitis Defined as Common Terminology Criteria for Adverse Events Version 4 Grade 2 or Higher Pneumonitis

Common Terminology Criteria for Adverse Events version 4, grade 2 or higher pneumonitis is defined as breathing problems after radiation treatment requiring medications for treatment (grade 2), oxygen use (grade 3), hospitalization (grade 4), or leading to death (grade 5). Clinical studies commonly report how many patients that develop pneumonitis as a result of radiation treatment, which is usually within the first 3 months after radiation.

Time frame: Up to 3 months

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Treatment	Radiation Pneumonitis Defined as Common Terminology Criteria for Adverse Events Version 4 Grade 2 or Higher Pneumonitis	17 Participants

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

Conditions

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Overall Survival (OS) Rate

Change in Pulmonary Function (Diffusing Capacity of the Lungs for Carbon Monoxide [DLCO])

Change in Pulmonary Function-forced Expiratory Volume in 1 Second (FEV1)

Local-Regional Progression as Defined by Response Evaluation Criteria In Solid Tumors (RECIST) Criteria

Progression-free Survival (PFS)

Radiation Pneumonitis Defined as Common Terminology Criteria for Adverse Events Version 4 Grade 2 or Higher Pneumonitis