18F-fluciclovine PET/MRI Imaging for the Detection of Tumor Recurrence After Radiation Injury to the Brain

Study Overview
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Brief Summary
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This phase I trial studies the ability and amount of fluciclovine positron emission tomography (PET) imaging needed to recognize tumors that have come back (recurrence) after brain injury from radiation therapy (radionecrosis) in patients with intracranial disease that has spread to other places in the body (metastatic). F-18 fluciclovine is a radiotracer that works by accumulating in tumor cells, making it easier to detect tumors. The results of this study may also help investigators understand all the ways that F-18 fluciclovine may affect patients.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine the static fluciclovine F18 (fluciclovine) PET imaging tumor-to-background ratios (TBRmax; TBRmean) which distinguish true tumor recurrence from radionecrosis in patients with intracranial metastatic disease previously treated with radiation therapy, and magnetic resonance imaging (MRI) findings suggesting recurrent disease, using histopathology as proof of disease. SECONDARY OBJECTIVES: I. To determine static fluciclovine PET standardized uptake value (SUV)peak, SUVmean values and metabolic tumor volumes (MTV) which distinguish true tumor recurrence from radionecrosis in patients with MRI findings suggesting recurrent disease, using serial MRI as a surrogate marker of disease. II. To determine early dynamic fluciclovine PET time activity curve values which distinguish true tumor recurrence from radionecrosis in patients with MRI findings suggesting recurrent disease, using histopathology or serial MRI as a marker of disease. III. To correlate the determined static fluciclovine PET SUVpeak, SUVmean, TBRmax, TBRmean, and MTV values with progression free survival. IV. In patients with true tumor progression, SUV values will be correlated with Ki67 staining on final pathology. OUTLINE: Patients receive fluciclovine intravenously (IV) and undergo brain dynamic PET/MRI imaging over 50 minutes. After completion of study, patients are followed up every 3 months for up to 1 year.

Official Title
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18F-Fluciclovine PET Discrimination of Radiation Injury to the Brain

Conditions
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Metastatic Intracranial Malignant Neoplasm, Recurrent Intracranial Neoplasm

Intervention / Treatment
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* Radiation: Dynamic Contrast-Enhanced Magnetic Resonance Imaging with Positron Emission Tomography
* Other: Fluciclovine F18


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical evidence of intracranial metastatic disease which underwent radiation and who presents with MRI findings suspicious for recurrent disease and/or radionecrosis (namely the 'index lesion') Exclusion Criteria: Contraindication to contrast enhanced MRI Females of child-bearing potential who are pregnant or lactating or who are not using adequate contraception (surgical, hormonal or double barrier, i.e. condom and diaphragm) Inability to lie still for 50 minutes during fluciclovine PET-MRI imaging Inability or refusal to consent Allergy or anaphylaxis to any of the reagents used in this study Inability or unwillingness to return for required visits and follow-up exams

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Diagnostic (18F-fluciclovine, PET/MRI imaging)<br>Patients receive fluciclovine IV and undergo brain dynamic PET/MRI imaging over 50 minutes. | Radiation: Dynamic Contrast-Enhanced Magnetic Resonance Imaging with Positron Emission Tomography<br>* Undergo PET-MRI imaging<br>* Other names: DCE-MRI/PET;Other: Fluciclovine F18<br>* Given IV<br>* Other names: GE-148 F-18;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor-to-background ratios (TBR)max and TBRmean thresholds | Will be estimated to delineate tumor progression from radionecrosis for use in future studies. The optimal TBRmax and TBRmean thresholds will be chosen as the threshold with the best cutpoint/threshold during a Receiver Operating Characteristics analysis corresponding to the maximum area under the curve (AUC) value when both the sensitivity and specificity are greater than 85%. | Up to 4 weeks post study registration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Static values for fluciclovine PET standardized uptake value (SUV)peak that distinguish true tumor recurrence from radionecrosis in patients with MRI findings suggesting recurrent disease | Determined using serial MRI as a surrogate marker of disease.The optimal SUVpeak, SUVmean and metabolic tumor volumes (MTV) values will be chosen as the threshold with the best cutpoint/threshold during a Receiver Operating Characteristics analysis corresponding to the maximum AUC value when both the sensitivity and specificity are greater than 85%. | Up to 4 weeks post study registration | 
| Static values for fluciclovine SUVmean that distinguish true tumor recurrence from radionecrosis in patients with MRI findings suggesting recurrent disease | Determined using serial MRI as a surrogate marker of disease. The optimal SUVmean values will be chosen as the threshold with the best cutpoint/threshold during a Receiver Operating Characteristics analysis corresponding to the maximum AUC value when both the sensitivity and specificity are greater than 85%. | Up to 4 weeks post study registration | 
| Static values for metabolic tumor volumes (MTV) that distinguish true tumor recurrence from radionecrosis in patients with MRI findings suggesting recurrent disease | Determined using serial MRI as a surrogate marker of disease. The optimal MTV values will be chosen as the threshold with the best cutpoint/threshold during a Receiver Operating Characteristics analysis corresponding to the maximum AUC value when both the sensitivity and specificity are greater than 85%. | Up to 4 weeks post study registration | 
| Incidence of adverse events | Will be graded using Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. | Every 3 months up to 1 year |