Study to Establish Image Interpretation Criteria for 18F Fluciclovine PET in Detecting Recurrent Brain Metastases (PURSUE)

Study Overview
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Brief Summary
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An Open-label, Single-arm, Single-dose, Prospective, Multicenter Phase 2b Study to Establish Image Interpretation Criteria for 18F-Fluciclovine Positron Emission Tomography (PET) in Detecting Recurrent Brain Metastases After Radiation Therapy

Official Title
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An Open-label, Single-arm, Single-dose, Prospective, Multicenter Phase 2b Study to Establish Image Interpretation Criteria for 18F-Fluciclovine Positron Emission Tomography (PET) in Detecting Recurrent Brain Metastases After Radiation Therapy

Conditions
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Brain Metastases

Intervention / Treatment
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* Drug: 18F fluciclovine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Previous history of solid tumor brain metastasis of any origin Histopathological confirmation of the primary solid tumor or a metastatic site Previous radiation therapy of brain metastatic lesion(s) A reference lesion considered by the site investigator to be equivocal for recurrent brain metastasis Patient requires further confirmatory diagnostic procedures to confirm brain MRI findings and is planned for craniotomy Exclusion Criteria: 1. Patients with a history of active hematological malignancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Positron Emission Tomography (PET) Imaging study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients<br>Single intravenous administration of 18F fluciclovine for PET Scan | Drug: 18F fluciclovine<br>* 18F fluciclovine injection, 185 MegaBecquerel (MBq) (5 Millicurie (mCi)) ± 20%, delivered as an intravenous bolus<br>* Other names: Axumin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds | 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. | 60 days | 
| Specificity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds | 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 | 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases Based on Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake | 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). | 60 days | 
| Specificity of Different Thresholds of Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake. | 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) | 60 days | 
| Treatment-emergent Adverse Events | 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. | From the time of administration of 18F fluciclovine until 1 day post-18F-fluciclovine administration. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent Brain Metastases, Diagnostic, Positron Emission Tomography (PET) Scan