Trial Outcomes & Findings for Study to Establish Image Interpretation Criteria for 18F Fluciclovine PET in Detecting Recurrent Brain Metastases (PURSUE) (NCT NCT04410367)
NCT ID: NCT04410367
Last Updated: 2025-07-20
Results Overview
Sensitivity is calculated as % of participants with positive histopathology who are classified as positive on their 18F fluciclovine PET (i.e. true positive). Each participant had one lesion, therefore results are representative of both subject and lesion level sensitivity. Three readers evaluated the PET scans to classify 18F fluciclovine uptake in study lesions according to 4 incremental categories: absent, mild, moderate or marked. Three different thresholds of 18F fluciclovine uptake were then applied to calculate the sensitivity: Mild or Higher Uptake, Moderate or Higher Uptake, Marked Uptake. As an example, for calculating sensitivity based on the threshold of Mild or Higher Uptake, all participants with positive histopathology, classified by a reader as having mild, moderate or marked 18F fluciclovine uptake, would be categorized as true positive. This calculation was then repeated on the other two threshold categories, to produce sensitivities at different thresholds.
COMPLETED
PHASE2
23 participants
60 days
2025-07-20
Participant Flow
Subjects with a history of brain metastases previously treated with primary, adjuvant, or repeat (salvage) radiation therapy, with a recent standard of care (SoC) brain magnetic resonance imaging (MRI) found to be equivocal for recurrent brain metastasis, and who met all the inclusion criteria and none of the exclusion criteria, were consented and enrolled. Subjects were screened between 28Oct2020 and 30Dec2021. Nine clinical research sites in the US participated in the study.
On-study site investigators prospectively annotated and measured the 'reference lesion' on a postradiation treatment MRI scan and on the SoC MRI brain scan to confirm eligibility. The 'reference lesion' was defined as the lesion which was Equivocal for recurrent metastasis on SoC MRI, Intended for pre-planned SoC craniotomy, and If \> 1 equivocal lesion was intended for resection, the largest of these lesions.
Participant milestones
| Measure |
18F-Fluciclovine Injection
Subjects who have been dosed with 18F-Fluciclovine, have an evaluable on-study PET scan, and an evaluable central histopathology report from the sample obtained from the SoC craniotomy.
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|---|---|
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Overall Study
STARTED
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23
|
|
Overall Study
Underwent 18F-fluciclovine PET
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23
|
|
Overall Study
COMPLETED
|
23
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Establish Image Interpretation Criteria for 18F Fluciclovine PET in Detecting Recurrent Brain Metastases (PURSUE)
Baseline characteristics by cohort
| Measure |
Patients
n=23 Participants
Single intravenous administration of 18F fluciclovine for PET Scan
18F fluciclovine: 18F fluciclovine injection, 185 MBq (5 mCi) ± 20%, delivered as an intravenous bolus
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|---|---|
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Age, Continuous
|
59.8 years
STANDARD_DEVIATION 11.88 • n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
15 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 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
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
20 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
23 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 60 daysPopulation: Sensitivity analysis (%) based on 10 subjects with positive lesions per standard of truth (central histopathological analysis).
Sensitivity is calculated as % of participants with positive histopathology who are classified as positive on their 18F fluciclovine PET (i.e. true positive). Each participant had one lesion, therefore results are representative of both subject and lesion level sensitivity. Three readers evaluated the PET scans to classify 18F fluciclovine uptake in study lesions according to 4 incremental categories: absent, mild, moderate or marked. Three different thresholds of 18F fluciclovine uptake were then applied to calculate the sensitivity: Mild or Higher Uptake, Moderate or Higher Uptake, Marked Uptake. As an example, for calculating sensitivity based on the threshold of Mild or Higher Uptake, all participants with positive histopathology, classified by a reader as having mild, moderate or marked 18F fluciclovine uptake, would be categorized as true positive. This calculation was then repeated on the other two threshold categories, to produce sensitivities at different thresholds.
Outcome measures
| Measure |
18F-Fluciclovine Injection
n=10 Participants
Subjects who have been dosed with 18F-Fluciclovine, have an evaluable on-study PET scan, and positive histopathology.
|
|---|---|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds
Mild or Higher Uptake = Positive : Central Reader 1
|
100 percentage of participants
Interval 69.2 to 100.0
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds
Mild or Higher Uptake = Positive : Central Reader 2
|
100 percentage of participants
Interval 69.2 to 100.0
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds
Moderate or Higher Uptake = Positive : Central Reader 1
|
100 percentage of participants
Interval 69.2 to 100.0
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds
Moderate or Higher Uptake = Positive : Central Reader 3
|
90 percentage of participants
Interval 55.5 to 99.8
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds
Marked Uptake = Positive : Central Reader 1
|
80 percentage of participants
Interval 44.4 to 97.5
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds
Marked Uptake = Positive : Central Reader 3
|
60 percentage of participants
Interval 26.2 to 87.8
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds
Mild or Higher Uptake = Positive : Central Reader 3
|
100 percentage of participants
Interval 69.2 to 100.0
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds
Moderate or Higher Uptake = Positive : Central Reader 2
|
100 percentage of participants
Interval 69.2 to 100.0
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds
Marked Uptake = Positive : Central Reader 2
|
40 percentage of participants
Interval 12.2 to 73.8
|
PRIMARY outcome
Timeframe: 60 daysPopulation: Specificity analysis (%) based on 13 subjects with negative lesions per standard of truth (central histopathological analysis).
Specificity is calculated as the % of participants with negative histopathology who are classified as negative on their 18F fluciclovine PET (i.e. true negative). Each participant had 1 lesion, therefore results are representative of both subject and lesion level specificity. 3 readers evaluated the PET scans to classify 18F fluciclovine uptake in study lesions according to 4 incremental categories: absent, mild, moderate or marked. 3 different thresholds of uptake were then applied to calculate the specificity: Mild or Higher Uptake, Moderate or Higher Uptake, Marked Uptake. Example, for calculating specificity based on the threshold of Moderate or Higher Uptake, all participants with negative histopath, classified by a reader as having absent or mild uptake (i.e. not classified by a reader as having moderate or marked uptake), would be categorized as true negative. This calculation was repeated on the other 2 threshold categories, to produce specificities at different thresholds
Outcome measures
| Measure |
18F-Fluciclovine Injection
n=13 Participants
Subjects who have been dosed with 18F-Fluciclovine, have an evaluable on-study PET scan, and positive histopathology.
|
|---|---|
|
Specificity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds
Mild or Higher Uptake = Positive : Central Reader 3
|
0 percentage of participants
Interval 0.0 to 24.7
|
|
Specificity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds
Moderate or Higher Uptake = Positive : Central Reader 1
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38.5 percentage of participants
Interval 13.9 to 68.4
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Specificity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds
Moderate or Higher Uptake = Positive : Central Reader 2
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30.8 percentage of participants
Interval 9.1 to 61.4
|
|
Specificity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds
Moderate or Higher Uptake = Positive : Central Reader 3
|
46.2 percentage of participants
Interval 19.2 to 74.9
|
|
Specificity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds
Mild or Higher Uptake = Positive : Central Reader 1
|
0 percentage of participants
Interval 0.0 to 24.7
|
|
Specificity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds
Mild or Higher Uptake = Positive : Central Reader 2
|
0 percentage of participants
Interval 0.0 to 24.7
|
|
Specificity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds
Marked Uptake = Positive : Central Reader 1
|
92.3 percentage of participants
Interval 64.0 to 99.8
|
|
Specificity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds
Marked Uptake = Positive : Central Reader 2
|
100 percentage of participants
Interval 75.3 to 100.0
|
|
Specificity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds
Marked Uptake = Positive : Central Reader 3
|
100 percentage of participants
Interval 75.3 to 100.0
|
SECONDARY outcome
Timeframe: 60 daysPopulation: Sensitivity analysis (%) based on 10 subjects with positive lesions per standard of truth.
Sensitivity calculated as %participants with positive histopath and positive on PET (i.e. true positive). Each participant had 1 lesion, results represent both subject and lesion level sensitivity. Sensitivity is calculated using positive PET classified by quantitative and dynamic measures. Quantitative measure is based on lesion standardized uptake value (SUV). Receiver Operating Characteristic (ROC) analysis of all participant lesion SUV was performed. ROC analyses was performed to select a SUV threshold for calculating sensitivity. Sensitivity calculation: participants with positive histopath and SUV = or \> threshold are positive on scan. Dynamic measure: 3 readers evaluated PET scans to classify uptake pattern based on 4 categories: Type 0, Type I, Type II, Type III. Sensitivity is calculated for each type of uptake pattern (example: calculating sensitivity based on Type I pattern, participants with positive histopath, classified as Type I, would be categorized as true positive).
Outcome measures
| Measure |
18F-Fluciclovine Injection
n=10 Participants
Subjects who have been dosed with 18F-Fluciclovine, have an evaluable on-study PET scan, and positive histopathology.
|
|---|---|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases Based on Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake
Quantitative SUV ≥ 4.8 = Positive : Central Reader 1
|
80 percentage of participants
Interval 44.4 to 97.5
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases Based on Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake
Quantitative SUV ≥ 4.8 = Positive : Central Reader 2
|
80 percentage of participants
Interval 44.4 to 97.5
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases Based on Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake
Quantitative SUV ≥ 4.8 = Positive : Central Reader 3
|
80 percentage of participants
Interval 44.4 to 97.5
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases Based on Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake
Dynamic Type 0 : Central Reader 2
|
0 percentage of participants
Interval 0.0 to 30.9
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases Based on Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake
Dynamic Type I: Central Reader 1
|
80 percentage of participants
Interval 44.4 to 97.5
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases Based on Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake
Dynamic Type I: Central Reader 3
|
100 percentage of participants
Interval 69.2 to 100.0
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases Based on Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake
Dynamic Type II: Central Reader 1
|
10 percentage of participants
Interval 0.3 to 44.5
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases Based on Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake
Dynamic Type II: Central Reader 2
|
10 percentage of participants
Interval 0.3 to 44.5
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases Based on Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake
Dynamic Type III: Central Reader 1
|
10 percentage of participants
Interval 0.3 to 44.5
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases Based on Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake
Dynamic Type III: Central Reader 2
|
0 percentage of participants
Interval 0.0 to 30.9
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases Based on Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake
Dynamic Type III: Central Reader 3
|
0 percentage of participants
Interval 0.0 to 30.9
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases Based on Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake
Dynamic Type 0: Central Reader 1
|
0 percentage of participants
Interval 0.0 to 30.9
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases Based on Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake
Dynamic Type 0 : Central Reader 3
|
0 percentage of participants
Interval 0.0 to 30.9
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases Based on Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake
Dynamic Type I: Central Reader 2
|
90 percentage of participants
Interval 55.5 to 99.8
|
|
Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases Based on Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake
Dynamic Type II: Central Reader 3
|
0 percentage of participants
Interval 0.0 to 30.9
|
SECONDARY outcome
Timeframe: 60 daysPopulation: Subjects who have been dosed with 18F-Fluciclovine, have an evaluable on-study PET scan, and negative histopathology.
Specificity is calculated as %participants with negative histopath and negative on PET (i.e. true negative). Each participant had 1 lesion, results represent both subject and lesion level specificity. Specificity is calculated using negative PET classified by quantitative and dynamic measures. Quantitative measure is based on lesion standardized uptake value (SUV). Receiver Operating Characteristic (ROC) analysis of all participant lesion SUV was performed. ROC analyses was performed to select a SUV threshold for calculating sensitivity. Specificity calculation: participants with negative histopath, SUV \< threshold are negative on scan. Dynamic measure: 3 readers evaluated PET scans to classify uptake pattern based on 4 categories: Type 0, Type I, Type II, Type III. Specificity is calculated for each type of uptake pattern (example, calculating specificity based on Type I pattern, participants with negative histopath, classified as Type I, would be categorized as true negative)
Outcome measures
| Measure |
18F-Fluciclovine Injection
n=13 Participants
Subjects who have been dosed with 18F-Fluciclovine, have an evaluable on-study PET scan, and positive histopathology.
|
|---|---|
|
Specificity of Different Thresholds of Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake.
SUV ≥ 4.8 : Central Reader 1
|
84.6 percentage of participants
Interval 54.6 to 98.1
|
|
Specificity of Different Thresholds of Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake.
SUV ≥ 4.8 : Central Reader 2
|
84.6 percentage of participants
Interval 54.6 to 98.1
|
|
Specificity of Different Thresholds of Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake.
SUV ≥ 4.8 : Central Reader 3
|
84.6 percentage of participants
Interval 54.6 to 98.1
|
|
Specificity of Different Thresholds of Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake.
Dynamic Type 0 : Central Reader 1
|
100 percentage of participants
Interval 75.3 to 100.0
|
|
Specificity of Different Thresholds of Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake.
Dynamic Type 0 : Central Reader 3
|
100 percentage of participants
Interval 75.3 to 100.0
|
|
Specificity of Different Thresholds of Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake.
Dynamic Type I : Central Reader 1
|
7.7 percentage of participants
Interval 0.2 to 36.0
|
|
Specificity of Different Thresholds of Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake.
Dynamic Type I : Central Reader 3
|
0 percentage of participants
Interval 0.0 to 24.7
|
|
Specificity of Different Thresholds of Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake.
Dynamic Type II : Central Reader 3
|
100 percentage of participants
Interval 75.3 to 100.0
|
|
Specificity of Different Thresholds of Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake.
Dynamic Type III : Central Reader 1
|
100 percentage of participants
Interval 75.3 to 100.0
|
|
Specificity of Different Thresholds of Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake.
Dynamic Type 0 : Central Reader 2
|
100 percentage of participants
Interval 75.3 to 100.0
|
|
Specificity of Different Thresholds of Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake.
Dynamic Type I : Central Reader 2
|
15.4 percentage of participants
Interval 1.9 to 45.5
|
|
Specificity of Different Thresholds of Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake.
Dynamic Type II : Central Reader 1
|
92.3 percentage of participants
Interval 64.0 to 99.8
|
|
Specificity of Different Thresholds of Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake.
Dynamic Type II : Central Reader 2
|
84.6 percentage of participants
Interval 54.6 to 98.1
|
|
Specificity of Different Thresholds of Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake.
Dynamic Type III : Central Reader 2
|
100 percentage of participants
Interval 75.3 to 100.0
|
|
Specificity of Different Thresholds of Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake.
Dynamic Type III : Central Reader 3
|
100 percentage of participants
Interval 75.3 to 100.0
|
SECONDARY outcome
Timeframe: From the time of administration of 18F fluciclovine until 1 day post-18F-fluciclovine administration.Safety will be assessed from data on the occurrence of one or more treatment-emergent Adverse Events from the time of intravenous administration of 18F fluciclovine until 1 day post-18F-fluciclovine administration.
Outcome measures
| Measure |
18F-Fluciclovine Injection
n=23 Participants
Subjects who have been dosed with 18F-Fluciclovine, have an evaluable on-study PET scan, and positive histopathology.
|
|---|---|
|
Treatment-emergent Adverse Events
Subjects reporting at least 1 TEAE
|
1 Participants
|
|
Treatment-emergent Adverse Events
Nervous System Disorders (Headache)
|
1 Participants
|
Adverse Events
18F-Fluciclovine Injection
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
18F-Fluciclovine Injection
n=23 participants at risk
Subjects who have been dosed with 18F-Fluciclovine, have an evaluable on-study PET scan, and an evaluable central histopathology report from the sample obtained from the SoC craniotomy.
|
|---|---|
|
Nervous system disorders
Headache
|
4.3%
1/23 • Number of events 1 • Safety was assessed from the time of 18F-fluciclovine administration until 1 day post18Ffluciclovine administration based on reported adverse events (AEs) and serious adverse events (SAEs); treatment emergent adverse events (TEAE).
|
Additional Information
Chief Medical Officer
Blue Earth Diagnostics, Ltd.
Results disclosure agreements
- Principal investigator is a sponsor employee Neither the INSTITUTION nor the INVESTIGATOR will submit for publication or public disclosure any publication or disclosure based on the results of the Study until after the first to occur of (a) publication of the multi-center clinical trial results; (b) notification by BED that the multi-center clinical trial submission is no longer planned; or (c) the eighteen (18) month anniversary of the completion or early termination of the multi-center clinical trial.
- Publication restrictions are in place
Restriction type: OTHER