Trial Outcomes & Findings for FLARE RT for Patients With Stage IIB-IIIB Non-small Cell Lung Cancer: Personalizing Radiation Therapy Using PET/CT and SPECT/CT Imaging (NCT NCT02773238)

NCT ID: NCT02773238

Last Updated: 2024-08-14

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 51 participants
• Primary outcome timeframe: At 2 years
• Results posted on: 2024-08-14

Participant Flow

Participant milestones

Measure	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
Overall Study STARTED	51
Overall Study COMPLETED	47
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Measure

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

Overall Study Lack of Efficacy

4

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Treatment n=51 Participants 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
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	30 Participants n=5 Participants
Age, Categorical >=65 years	21 Participants n=5 Participants
Age, Continuous	63.2 years STANDARD_DEVIATION 8.1 • n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants
Sex: Female, Male Male	23 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	36 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants
Region of Enrollment United States	51 Participants n=5 Participants

PRIMARY outcome

Timeframe: At 2 years

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

Outcome measures

Measure

Treatment n=51 Participants 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

Overall Survival (OS) Rate

54.2 percentage of patients Interval 41.8 to 70.4

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure

Treatment n=51 Participants 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

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

17 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure

Treatment n=51 Participants 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

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

12.2 percentage of patients Interval 4.9 to 23.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure

Treatment n=51 Participants 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

Progression-free Survival (PFS)

53.1 percentage of patients Interval 40.9 to 69.0

SECONDARY outcome

Timeframe: 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.

Pulmonary function tests (FEV1, liters) will be performed and change over time will be evaluated.

Outcome measures

Measure

Treatment n=45 Participants 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

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

-0.15 liters Standard Deviation 0.09

SECONDARY outcome

Timeframe: Baseline to 3 months post-radiation therapy

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

Pulmonary function tests (DLCO, % predicted) will be performed and change over time will be evaluated.

Outcome measures

Measure

Treatment n=45 Participants 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

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

-8 percentage of predicted lung function Standard Deviation 5.2

Adverse Events

Treatment

Serious events: 6 serious events

Other events: 49 other events

Deaths: 24 deaths

Serious adverse events

Measure	Treatment n=51 participants at risk 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
Respiratory, thoracic and mediastinal disorders Pneumonitis Grade 3+	7.8% 4/51 • Number of events 4 • Adverse events were collected during radiation treatment weekly during physician visits, and then monthly after radiation treatment was completed for 3 months. CTCAE v4 was used to grade adverse events for up to 3 months after completion of radiation. Survival was monitored for up to 2 years after end of radiation.
Gastrointestinal disorders Esophagitis Grade 3+	3.9% 2/51 • Number of events 2 • Adverse events were collected during radiation treatment weekly during physician visits, and then monthly after radiation treatment was completed for 3 months. CTCAE v4 was used to grade adverse events for up to 3 months after completion of radiation. Survival was monitored for up to 2 years after end of radiation.

Other adverse events

Measure	Treatment n=51 participants at risk 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
Respiratory, thoracic and mediastinal disorders Pneumonitis Grade 2	29.4% 15/51 • Number of events 15 • Adverse events were collected during radiation treatment weekly during physician visits, and then monthly after radiation treatment was completed for 3 months. CTCAE v4 was used to grade adverse events for up to 3 months after completion of radiation. Survival was monitored for up to 2 years after end of radiation.
Gastrointestinal disorders Esophagitis Grade 2	58.8% 30/51 • Number of events 30 • Adverse events were collected during radiation treatment weekly during physician visits, and then monthly after radiation treatment was completed for 3 months. CTCAE v4 was used to grade adverse events for up to 3 months after completion of radiation. Survival was monitored for up to 2 years after end of radiation.
Skin and subcutaneous tissue disorders Dermatitis Grade 2	9.8% 5/51 • Number of events 5 • Adverse events were collected during radiation treatment weekly during physician visits, and then monthly after radiation treatment was completed for 3 months. CTCAE v4 was used to grade adverse events for up to 3 months after completion of radiation. Survival was monitored for up to 2 years after end of radiation.
General disorders Fatigue Grade 2	11.8% 6/51 • Number of events 6 • Adverse events were collected during radiation treatment weekly during physician visits, and then monthly after radiation treatment was completed for 3 months. CTCAE v4 was used to grade adverse events for up to 3 months after completion of radiation. Survival was monitored for up to 2 years after end of radiation.

Additional Information

Dr. Jing Zeng

University of Washington

Phone: 206-598-4110

Email: jzeng13@uw.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place