18F-Fluciclovine PET and Multiparametric MR Imaging

Differentiating Brain Tumor Recurrence From Treatment-Induced Necrosis Using 18F-Fluciclovine (Anti-18f-facbc) PET and Multiparametric MR Imaging

The purpose of the study is to investigate the use of the investigational agent Axumin (fluciclovine-F18) with PET/CT imaging in combination with standard MR imaging to detect remaining or recurrent brain tumor.

Study Overview

• Status: Recruiting
• Conditions: Brain Tumor, Recurrent, Adult
• Intervention / Treatment: Drug: PET/CT with F-Fluciclovine (Axumin)

Detailed Description

Methods:

Patients with recurrent enhancing mass on MRI in the side of a diagnosed and treated high grade glioma or metastatic brain tumor and consenting to study protocol will undergo 18F-Fluciclovine PET/CT imaging once prior to surgery for brain tumor recurrence. Surgery for recurrent brain tumor will follow standard of care treatment that includes either biopsy of the region or interest or as complete as possible tumor resection followed by histopathological analysis. Outcome evaluation will be analysis of tumor histology and imaging results, comparison of MRI, MRSI, and 18F-Fluciclovine imaging and relationship of imaging findings with histopathology and anatomical location of recurrent tumor.

Study Objectives

1. In this study, we will investigate the potential of 18F-fluciclovine to aid the visualization of residual or recurrent gliomas as depicted by 18F-Fluciclovine PET imaging compared to standard MRI sequences [T1 weighted imaging (T1WI) with contrast, diffusion weighted imaging (DWI), perfusion weighted imaging (PWI), T2 weighted fluid attenuated inversion recovery (T2 FLAIR)] using 3D image fusion.
2. To assess the residual or recurrent of glioma as depicted by 3D short echo time MR spectroscopic imaging (MRSI) using metabolic tumor markers such as elevated choline, myo-Inositol and lipids and reduced N-acetyl-aspartate (NAA) compared to standard MRI sequences (T1WI with contrast, PWI, T2 FLAIR) using 3D image fusion before neurosurgical intervention.
3. To spatially register the residual or recurrent glioma as depicted by 18F-Fluciclovine PET imaging with MR T1WI, DWI, PWI, and 3D MRSI to a) quantitate (SUVmax, SUVmean, ADCmean, rCBV, Cho, NAA, lipids, Cho/Cr, Cho/NAA) and correlate areas of PET+, T1WI+ and MRSI+ areas and b) characterize different metabolic profiles measured with MRSI in areas of glioma infiltration depicted by PET imaging and MRI.
4. Biopsy and pathology confirmation of tumor vs treatment-induced necrosis in spatially registered areas of interest will be performed.

Safety analysis Although 18F-Axumin™ is an FDA approved PET imaging agent for biological recurrent prostate cancer with extensive safety and toxicity data already documented, all patients will be monitored closely for adverse reactions after administration.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Warren Boling, MD; Phone Number: 909-558-4419; Email: wboling@llu.edu
• Study Contact Backup: Name: Brenda Bartnik-Olson, PhD; Phone Number: 47809 909-558-4000; Email: BBartnik@llu.edu

Study Locations

• United States
  • California
    • Loma Linda, California, United States, 92354
      • Recruiting
      • Loma Linda University Cancer Center
      • Contact: Warren Boling, MD; Phone Number: 909-558-4419; Email: wboling@llu.edu
      • Contact: Barbara Holshouser, PhD; Phone Number: 47809 909-558-4000; Email: bholshouser@llu.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with prior histological confirmation of glioma or metastatic brain tumor evaluated for tumor recurrence or radiation changes after initial treatment of surgery, external beam radiation and / or chemotherapy with temozolamide.
2. Male and female
3. Ages 18 or greater

Exclusion Criteria:

1. Patient diagnosis with glioma or metastatic brain tumor but prior to surgery, external beam radiation and /or chemotherapy
2. Women who were pregnant, breast feeding, or possibly pregnant.
3. Patients with hepatic or renal dysfunction.
4. Patients with MRI contraindications (i.e. pacemakers, non-MR compatible devices).
5. Patients with a history of drug hypersensitivity to 18F-Fluciclovine.

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: Axumin (fluciclovine-F18) PET/CT scan; Axumin (fluciclovine-F18) PET/CT scan to evaluate possible glioma recurrence to help differentiate scar (fake recurrence) from true tumor recurrence

Drug: PET/CT with F-Fluciclovine (Axumin); Comparison between PET/CT, MRI / MRS imaging, and biopsy histopathology. Data from each modality will be analyzed separately as described above to determine tumor recurrence and/or presence of radiation changes. Different metabolic profiles measured in areas of imaging changes and depicted by PET imaging will be characterized. Biopsy locations from stereotactic MRI data will be co-localized with PET/CT and MRSI to correlate biopsy histopathology with MRI+, MRSI+ and PET+ lesion data.; Other Names: Axumin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
18F-Fluciclovine	Investigate the potential of 18F-fluciclovine to aid the visualization of residual or recurrent gliomas as depicted by 18F-Fluciclovine PET imaging compared to standard MRI sequences [T1 weighted imaging (T1WI) with contrast, diffusion weighted imaging (DWI), perfusion weighted imaging (PWI), T2 weighted fluid attenuated inversion recovery (T2 FLAIR)] using 3D image fusion.	2 years
3D short echo time MR spectroscopic imaging (MRSI)	Using metabolic tumor markers such as elevated choline, myo-Inositol and lipids and reduced N-acetyl-aspartate (NAA) compared to standard MRI sequences (T1WI with contrast, PWI, T2 FLAIR) using 3D image fusion before neurosurgical intervention.	2 years
18F-Fluciclovine PET imaging with MR T1WI, DWI, PWI, and 3D MRSI	Quantitate (SUVmax, SUVmean, ADCmean, rCBV, Cho, NAA, lipids, Cho/Cr, Cho/NAA) and correlate areas of PET+, T1WI+ and MRSI+ areas and b) characterize different metabolic profiles measured with MRSI in areas of glioma infiltration depicted by PET imaging and MRI.	2 years
Biopsy and pathology	Confirmation of tumor vs treatment-induced necrosis in spatially registered areas of interest will be performed.	2 years

Collaborators and Investigators

• Sponsor: Loma Linda University
• Collaborators: Blue Earth Diagnostics
• Investigators: Principal Investigator: Warren Boling, MD, Loma Linda University Medical Center

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): August 24, 2020
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: April 19, 2019
• First Submitted That Met QC Criteria: April 19, 2019
• First Posted (Actual): April 24, 2019

Study Record Updates

• Last Update Posted (Actual): August 29, 2023
• Last Update Submitted That Met QC Criteria: August 28, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Neoplasms
• Other Study ID Numbers: 5180227

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes