Study to Establish the Diagnostic Performance of 18F Fluciclovine PET in Detecting Recurrent Brain Metastases (REVELATE)

An Open-label, Single-arm, Single-dose, Prospective, Multicenter Phase 3 Study to Establish the Diagnostic Performance of 18F-Fluciclovine Positron Emission Tomography (PET) in Detecting Recurrent Brain Metastases After Radiation Therapy

An open-label, single dose, single arm, prospective, multicenter Phase 3 study to establish the diagnostic performance of 18F fluciclovine positron emission tomography (PET) in detecting recurrent brain metastases after radiation therapy

Study Overview

• Status: Completed
• Conditions: Brain Metastases
• Intervention / Treatment: Drug: 18F fluciclovine

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center
  • California
    • San Francisco, California, United States, 94118
      • University of California, San Francisco
    • Santa Monica, California, United States, 90404
      • John Wayne Cancer Institute at Providence St. John's Health Center
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale School of Medicine
  • Florida
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute at Baptist Health, Inc.
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Medical College of Georgia, Augusta University
  • Louisiana
    • New Orleans, Louisiana, United States, 70131
      • Ochsner Clinic Foundation
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Rogel Cancer Center
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine-Center for Clinical Imaging Research
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • University Hospital Cleveland
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Health System
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Center for Quantitative Cancer Imaging at Huntsman Cancer Institute
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virgina University Cancer Institute

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, or 2 if this is an acute deterioration
2. Previous history of solid tumor brain metastasis of any origin
3. Histopathological confirmation of the primary solid tumor or a metastatic site within 4 years
4. Previous radiation therapy of brain metastatic lesion(s)
5. A reference lesion considered by the site investigator to be equivocal for recurrent brain metastasis
6. Patient requires further confirmatory diagnostic procedures to confirm brain MRI findings and is planned for biopsy/neurosurgical intervention as standard of care (SoC) or clinical follow-up as SoC

Exclusion Criteria:

1. Patients with a history of active hematological malignancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients; Single intravenous administration of 18F fluciclovine for PET Scan	Drug: 18F fluciclovine; 18F fluciclovine injection, 185 MBq (5 mCi) ± 20%, delivered as an intravenous bolus; Other Names: Axumin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) Subject Level	Subject-level PPA and NPA (equivalent to sensitivity and specificity, respectively) of 18F-fluciclovinePET in detecting recurrent brain metastases.	MRI for anatomical correlation within 3 days of IMP and PET scan, followed by surgical intervention (if applicable) post-PET scan and follow up through 6 months after PET scan.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subject Level Positive Predictive Value (PPV) and Negative Predictive Value (NPV)	Subject-level PPV and NPV of 18F-fluciclovine PET for detecting recurrent brain metastases	MRI for anatomical correlation within 3 days of IMP and PET scan, followed by surgical intervention (if applicable) post-PET scan and follow up through 6 months after PET scan.
Lesion-level Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA)	To assess lesion-level PPA & NPA diagnostic performance of 18F-fluciclovine PET in detecting recurrent brain metastases.	MRI for anatomical correlation within 3 days of IMP and PET scan, followed by surgical intervention (if applicable) post-PET scan and follow up through 6 months after PET scan.
Lesion-level Positive Predictive Value (PPV) and Negative Predictive Value (NPV)	To assess lesion-level PPV & NPV diagnostic performance of 18F-fluciclovine PET in detecting recurrent brain metastases.	MRI for anatomical correlation within 3 days of IMP and PET scan, followed by surgical intervention (if applicable) post-PET scan and follow up through 6 months after PET scan.
Subject-level Positive Percent Agreement (PPA) & Negative Percent Agreement (NPA) Diagnostic Performance of Fluciclovine (18F) PET in Detecting Recurrent Brain Metastases in Different Clinical Settings - Tumor Type	Sub-group analyses of subject-level PPA & NPA of fluciclovine (18F) PET, according to primary tumor type.	MRI for anatomical correlation within 3 days of IMP and PET scan, followed by surgical intervention (if applicable) post-PET scan and follow up through 6 months after PET scan.
Subject-level Positive Predictive Value (PPV) & Negative Predictive Value (NPV) Diagnostic Performance of Fluciclovine (18F) PET in Detecting Recurrent Brain Metastases in Different Clinical Settings - Tumor Type	Sub-group analyses of subject-level PPV & NPV of fluciclovine (18F) PET, according to primary tumor type.	MRI for anatomical correlation within 3 days of IMP and PET scan, followed by surgical intervention (if applicable) post-PET scan and follow up through 6 months after PET scan.
Subject-level Positive Percent Agreement (NPA) & Negative Percent Agreement (NPA) Diagnostic Performance of Fluciclovine (18F) PET in Detecting Recurrent Brain Metastases in Different Clinical Settings - Concurrent Immunotherapy	Sub-group analyses of subject-level PPA & NPA of fluciclovine (18F) PET, according to concurrent immunotherapy.	MRI for anatomical correlation within 3 days of IMP and PET scan, followed by surgical intervention (if applicable) post-PET scan and follow up through 6 months after PET scan.
Subject-level Positive Predictive Value (PPV) & Negative Predictive Value (NPV) Diagnostic Performance of Fluciclovine (18F) PET in Detecting Recurrent Brain Metastases in Different Clinical Settings - Concurrent Immunotherapy	Sub-group analyses of subject-level PPV & NPV of fluciclovine (18F) PET, according to Concurrent Immunotherapy.	MRI for anatomical correlation within 3 days of IMP and PET scan, followed by surgical intervention (if applicable) post-PET scan and follow up through 6 months after PET scan.
Clinical Usefulness	Number of days taken by the site to establish presence/absence of metastasis by clinical follow-up.	Follow up through 6 months after PET scan.
Clinical Usefulness	Proportion of subjects with additional metastases identified on fluciclovine (18F) PET in addition to SoC brain MRI	Follow up through 6 months after PET scan.
Clinical Usefulness	Proportion of subjects whose prospective diagnostic management plan changed following fluciclovine (18F) PET.	Follow up through 6 months after PET scan.
Inter-reader Reproducibility	Pairwise comparisons of the central reads for the 3 readers (i.e. Reader 1 vs Reader 2, Reader 1 vs Reader 3, and Reader 2 vs Reader 3) at the subject-level. The percentage of results in agreement (i.e. Positive [1st reader] / Positive [2nd reader], Negative/Negative) is presented.	PET Scan Day 1
Intra-reader Reproducibility	Pairwise comparisons of the initial read vs re-read of a subset of PET scans for each reader at the subject-level. The percentage of results in agreement (i.e. Positive [initial read] / Positive [re-read], Negative/Negative) is presented.	PET Scan Day 1
Assess the Safety of Fluciclovine (18F) Injection in the Subject Population, Blood Pressure	Treatment-emergent adverse events (TEAEs) following 18F-fluciclovine injection in the subject population.	The vital signs collected between 5 to 60 minutes before and after the PET scan.
Assess the Safety of Fluciclovine (18F) Injection in the Subject Population, Heart Rate	Treatment-emergent adverse events (TEAEs) following 18F-fluciclovine injection in the subject population.	The vital signs collected between 5 to 60 minutes before and after the PET scan.
Assess the Safety of Fluciclovine (18F) Injection in the Subject Population, Respiratory Rate	Treatment-emergent adverse events (TEAEs) following 18F-fluciclovine injection in the subject population.	The vital signs collected between 5 to 60 minutes before and after the PET scan.
Assess the Safety of Fluciclovine (18F) Injection in the Subject Population, Body Temperature	Treatment-emergent adverse events (TEAEs) following 18F-fluciclovine injection in the subject population.	The vital signs collected between 5 to 60 minutes before and after the PET scan.

Collaborators and Investigators

• Sponsor: Blue Earth Diagnostics
• Collaborators: Precision For Medicine

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.

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2020
• Primary Completion (Actual): June 5, 2023
• Study Completion (Actual): June 5, 2023

Study Registration Dates

• First Submitted: May 27, 2020
• First Submitted That Met QC Criteria: May 27, 2020
• First Posted (Actual): June 1, 2020

Study Record Updates

• Last Update Posted (Estimated): August 28, 2025
• Last Update Submitted That Met QC Criteria: August 26, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Diagnostic; Recurrent Brain Metastases; Positron Emission Tomography (PET) Scan
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Pathological Conditions, Signs and Symptoms; Disease; Brain Neoplasms; fluciclovine F-18
• Other Study ID Numbers: BED-FLC-312

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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