18F-Fluciclovine PET to Distinguish Tumor Progression From Radiation Necrosis

A Prospective Pilot to Evaluate the Diagnostic Assessment of 18F-Fluciclovine Positron Emission Tomography to Distinguish Tumor Progression From Radiation Necrosis Following Stereotactic Radiosurgery for Brain Metastases

The purpose of this study is to evaluate whether 18F-fluciclovine PET/CT of the brain, is able to distinguish radiation necrosis from tumor progression in cases where MRI is inconclusive.

18F-fluciclovine is an FDA approved radioactive diagnostic agent and is injected into the participant and then taken up by cancer cells, which can then be visualized with a PET/CT scan. 18F-fluciclovine is FDA approved for the detection of recurrent prostate cancer, but is still investigational for the purposes of this study.

Study Overview

• Status: Completed
• Conditions: Secondary Malignant Neoplasm of Brain and Cerebral Meninges
• Intervention / Treatment: Drug: 18F-fluciclovine; Device: PET/CT of the brain

Detailed Description

The primary objective of this study is to estimate the accuracy of 18F-fluciclovine PET in distinguishing radiation necrosis from tumor progression. Accuracy will be assessed via receiver operating characteristic curve analysis, as well as by calculating sensitivity and specificity.

Secondary objectives of this study are to assess which factors may influence accuracy of 18Ffluciclovine PET in distinguishing radiation necrosis from tumor progression and to compare the accuracy of each of the qualitative and quantitative metrics.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must have a confirmed diagnosis of brain metastases.
• Subjects must have received prior intracranial SRS at least once for brain metastases. Prior WBRT is allowed.
• Subjects must have had a clinical tumor protocol MRI of the brain including a DSC-MR perfusion sequence, which is equivocal for radiation necrosis versus tumor progression within 30 days of treatment scan. "Equivocal" will be defined as being inconclusive for radiation necrosis versus tumor progression as determined by the study neuroradiologist.
• Physician assessed life expectancy of ≥ 6 months.
• Subjects must have the ability to understand and the willingness to sign a written informed consent document.
• For women of childbearing potential, a negative serum pregnancy test within 14 days of registration is required.

Exclusion Criteria:

• Subjects who have experienced a prior anaphylaxis reaction to 18Ffluciclovine are not eligible.
• Females pregnant at the expected time of 18F-fluciclovine administration are not eligible due to potential harm to the fetus from exposure to radiation. Women who could be pregnant require a negative pregnancy test to be eligible.
• Women who are breast feeding at the expected time of 18F-fluciclovine administration are not eligible due to potential harm to the infant from exposure to radiation.
• Subjects contraindicated for MRI.
• Subjects unable or unwilling to comply with study requirements are not eligible.
• Major medical illness or psychiatric impairments, which in the investigator's opinion, will prevent completion of protocol therapy and/or preclude informed consent.
• Brain metastases from primary lymphoma, germ cell tumor, or small cell carcinoma.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: 18F-fluciclovine PET/CT of the brain; Arm includes participants with a known diagnosis of brain metastases who have undergone prior intracranial SRS and whose MRI brain scan is equivocal for radiation necrosis versus tumor progression. Participants will undergo 18F-fluciclovine PET/CT of the brain. Qualitative and quantitative metrics will be documented at the time of image acquisition. Qualitative image assessment will be performed independently by 3 separate physicians.

Drug: 18F-fluciclovine; A single dose of 18F-fluciclovine will be administered intravenously for PET/CT imaging. The standard 10 mCi dose will be used for this study.; Device: PET/CT of the brain; Each subject will undergo 18F-fluciclovine PET/CT of the brain which will be performed ≤ 30 days from equivocal MRI brain

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy of 18F-fluciclovine PET as measured by area under the ROC curve (AUC)	The accuracy of 18F-fluciclovine PET in distinguishing radiation necrosis from tumor progression will be reported. Accuracy will be assessed via receiver operating characteristic curve analysis.	Up to 1 year from start of study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
18F-fluciclovine uptake in lesions, compared to normal brain tissue.	18F-fluciclovine uptake in lesions will be reported in comparison to normal brain tissue.	Up to 1 year from start of study
Sensitivity and specificity of 18F-fluciclovine PET	Sensitivity and specificity of 18F-fluciclovine PET diagnostic procedure	Up to 1 year from start of study

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Investigators: Principal Investigator: Samuel T Chao, MD, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer 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): July 2, 2019
• Primary Completion (ACTUAL): March 1, 2021
• Study Completion (ACTUAL): March 1, 2021

Study Registration Dates

• First Submitted: April 25, 2019
• First Submitted That Met QC Criteria: April 25, 2019
• First Posted (ACTUAL): April 29, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 5, 2021
• Last Update Submitted That Met QC Criteria: May 3, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms; Brain Neoplasms; Necrosis
• Other Study ID Numbers: CASE2319

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: Yes
• product manufactured in and exported from the U.S.: Yes