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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Intracranial Malignant Neoplasm; Recurrent Intracranial Neoplasm
• Intervention / Treatment: Radiation: Dynamic Contrast-Enhanced Magnetic Resonance Imaging with Positron Emission Tomography; Other: Fluciclovine F18

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Recruiting
      • Mayo Clinic in Florida
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Daniel M. Trifiletti, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with intracranial metastatic disease (brain tumor) that has been treated with radiation therapy.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Diagnostic (18F-fluciclovine, PET/MRI imaging); 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; Undergo PET-MRI imaging; Other Names: DCE-MRI with PET; DCE-MRI/PET; Other: Fluciclovine F18; Given IV; Other Names: (18F)Fluciclovine; (18F)GE-148; 18F-Fluciclovine; [18F]FACBC; Anti-(18f)FABC; Anti-1-Amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid; Anti-[18F] FACBC; Axumin; Fluciclovine (18F); FLUCICLOVINE F-18; GE-148 (18F); GE-148 F-18

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early dynamic fluciclovine PET time-activity curve values which distinguish true tumor recurrence from radionecrosis	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
Correlation of static fluciclovine PET SUVpeak, SUVmean, TBRmax, TBRmean, and MTV values with progression free survival	Differences in progression free survival time between patient groups based on the determined thresholds will be analyzed via Kaplan-Meier methods.	Up to 1 year after completion of PET/MR imaging
Correlation of SUV values with Ki67 staining	In patients with true tumor progression, SUV values will be correlated with Ki67 staining on final pathology. Spearman correlation analysis will be performed to determine if a relationship exists between SUV values and Ki67 staining values in patients with tumor progression.	Up to 4 weeks post study registration

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: Blue Earth Diagnostics, Inc
• Investigators: Principal Investigator: Daniel M. Trifiletti, M.D., Mayo Clinic

Publications and helpful links

General Publications

• Kotecha R, Aboian M, Nabavizadeh SA, Parent EE, Trifiletti DM, Chao ST. Letter regarding "Contribution of PET imaging to radiotherapy planning and monitoring in glioma patients-a report of the PET/RANO group": 18F-fluciclovine and target volume delineation. Neuro Oncol. 2021 Aug 2;23(8):1408-1409. doi: 10.1093/neuonc/noab097. No abstract available.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2020
• Primary Completion (Estimated): August 15, 2025
• Study Completion (Estimated): August 15, 2026

Study Registration Dates

• First Submitted: June 29, 2020
• First Submitted That Met QC Criteria: July 6, 2020
• First Posted (Actual): July 8, 2020

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 22, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Wounds and Injuries; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms; Brain Neoplasms; Radiation Injuries
• Other Study ID Numbers: MC1975 (Other Identifier: Mayo Clinic in Florida); NCI-2020-04564 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 16-002518 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No