FDG and FDOPA PET Demonstration of Functional Brain Abnormalities

• ClinicalTrials.gov Identifier: NCT04315584
• Recruitment Status: Recruiting
• First Posted: March 19, 2020
• Last Update Posted: March 24, 2020
• Sponsor: University of Virginia
• Information provided by (Responsible Party): Bijoy Kundu, University of Virginia

Study Description

Brief Summary:

The purpose of this pilot study will be to conduct a clinical trial using a time-of-flight PET scanner and MRI scanner to test an improved method for differentiating tumor recurrence from radiation necrosis in glioblastoma patients. We will attempt to do so by performing a static and dynamic FDG-PET scan, a static and dynamic FDOPA-PET scan, and a multiparametric MRI scan - then comparing the results with surgical pathology and static FDG-PET scans. We hypothesize that the new quantitative kinetic analytical methods using FDOPA in combination with FDG will provide crucial functional information to distinguish recurrent tumors from treatment-induced radiation changes in patients with treated brain neoplasms. This is important for improving patient outcomes by allowing treating physicians to more accurately tailor treatments. Furthermore, dynamic FDG and FDOPA PET will be combined with high resolution anatomic and physiologic MRI in order to develop a multimodal multiparametric approach for differentiating tumor recurrence from treatment effect.

Condition or disease	Intervention/treatment	Phase
Glioblastoma	Procedure: Positron Emission Tomography; Procedure: Computed Tomography; Procedure: Multiparametric Magnetic Resonance Imaging Scan; Radiation: Fludeoxyglucose F-18; Radiation: fluorine F 18 fluorodopa	Early Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

I. The primary objective will be to evaluate the diagnostic accuracy of Dynamic PET imaging in differentiating tumor recurrence from treatment effect (radiation necrosis or pseudoprogression) in patients previously treated with chemo-radiation therapy for primary high grade gliomas. This will be accomplished by examining the concordance between the Dynamic PET imaging prediction and the criterion standard, which will be based on either surgical pathology or an integrated clinical/MRI determination within a 3-6 month interval after Dynamic PET imaging.

SECONDARY OBJECTIVES:

I. The diagnostic accuracy of Static PET imaging, advanced MRI, and advanced MRI + Dynamic PET imaging in differentiating tumor recurrence from radiation-induced necrosis in high grade glioma patients will be examined in the same exact way as just outlined for Dynamic PET imaging.

OUTLINE:

Subjects receive 18FDG (first scan) and (18)F-FDOPA (2-14 days from the first scan) intravenously (IV) slowly over a period of 15-20 seconds and then undergo dynamic PET scans over a period of 60-90 minutes. CT scans on the subjects are performed before the dynamic PET scans for 5 minutes. Subjects also undergo MRI brain examinations just prior to the FDOPA scan over a period of 1 hour, which includes T1 weighed, T1 weighted contrast enhanced, T2 weighted, Diffusion tensor imaging, MR spectroscopy, and Dynamic susceptibility contrast perfusion weighted (DSC-PWI) imaging.

Study Design

• Study Type: Interventional
• Estimated Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: All 5 study subjects will undergo the same procedures.
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: FDG and FDOPA PET Demonstration of Functional Brain Abnormalities
• Estimated Study Start Date: March 15, 2020
• Estimated Primary Completion Date: December 20, 2023
• Estimated Study Completion Date: June 20, 2024

Arms and Interventions

Arm

Intervention/treatment

Experimental: Diagnostic; Study subjects will receive 18FDG via an IV before undergoing one PET/CT scan over 60 minutes. They will then receive an IV injection of Gadovist for contrast before undergoing a multiparametric MRI scan. Subjects will also receive (18)F-FDOPA via an IV before undergoing another PET/CT scan over 60 minutes.

Procedure: Positron Emission Tomography; Undergo PET/CT Scans; Other Names: PET; PET Scan; Positron Emission Tomography Scan; Medical Imaging, Positron Emission Tomography; Procedure: Computed Tomography; Undergo PET/CT Scans; Other Names: CT; CT Scan; Computerized Axial Tomography; CAT; CAT scan; Procedure: Multiparametric Magnetic Resonance Imaging Scan; Undergo a multiparametric MRI scan; Other Names: mpMRI; multiparametric MRI; Radiation: Fludeoxyglucose F-18; IV (intravenous) administration of radiotracer; Other Names: FDG; 18 FDG; fludeoxyglucose F 18; 2-F18-fluoro-2-deoxy-D-glucose; 2-F18-fluoro-2-deoxyglucose; Radiation: fluorine F 18 fluorodopa; IV (intravenous) administration of radiotracer; Other Names: 18F-6- L-fluorodopa; 18F-DOPA; 18F-FDOPA; 3,4-dihydroxy-6-(18)F-fluoro-l-phenylalanine; L-6-[ 18F]fluoro-3, 4-dihydroxyphenylalanine; (18)F-FDOPA

Outcome Measures

Primary Outcome Measures :

1. Quantitative parametric maps indicating differences in rates of glucose and amino acid uptake (Ki) obtained from dynamic FDG and FDOPA scans respectively. [ Time Frame: Up to 6 months ]
   Will be derived from PET/CT scan imaging.
2. Quantitative parametric maps indicating differences in details (d) components of the wavelet transform analysis, d6 and d8, based on established tumor feature criterions. [ Time Frame: Up to 6 months ]
   Will be derived from MRI brain scan imaging.
3. Semi-quantitative standardize uptake value (SUV) parametric maps based on static PET scans (last 20 minutes of the dynamic PET scans). [ Time Frame: Up to 6 months ]
   Will be derived from PET/CT scan imaging.
4. MRI brain metrics [ Time Frame: Up to 6 months ]
   Including anatomic assessment based on T1, T2, and contrast enhanced T1 weighted imaging, MR spectroscopy data (choline, creatinine, and N-acetyl acetate peak integrals and ratios), MR perfusion data (relative cerebral blood volume), and diffusion tensor imaging data (apparent diffusion coefficient, fractional anisotropy)
5. Surgical pathology or 3-6 month interval multidisciplinary clinical evaluation. [ Time Frame: Up to 6 months ]
   To be compared with the imaging analyses for comparing ability to differentiate tumor recurrence from radiation necrosis.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Age > 18
• Known or suspected recurrent malignant brain tumors
• Radiographic worsening reported on MRI shortly (within 3 months) after completion of radiation and temozolomide therapy
• Able to lie flat and/or still for a minimum of 60 minutes
• Willingness and ability to comply with scheduled visits and study procedures
• Patients who have a clinical indication for a PET-CT
• If female, patient must be postmenopausal or surgically sterile

Exclusion Criteria:

- Conditions that preclude a clinical brain FDG PET study, including: Consumption of liquids with sugar and/or caffeine prior to the study, Blood glucose levels over 150 mg/mL, Eating or drinking calories of any type within 4 hours of radiotracer injection, Hyperinsulinemia, Patients who for any reason cannot tolerate lying supine for 60 minutes

• Conditions that preclude a FDOPA PET study, including: Consuming a diet that is NOT low in protein after the previous evening meal
• Tumor located in the striatum
• Changes in medication (new prescriptions or change in dosages) between visits 1 and 2
• Pregnant, nursing, or lactating
• Women of childbearing potential (premenopausal female capable of becoming pregnant), which also includes:

women on oral, injectable, or mechanical contraceptives, women who are single, women whose male partners have been vasectomized or whose male partners have received or are utilizing mechanical contraceptive devices

• Weight > 450 lbs
• Known allergic reactions to 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (18F-FDOPA) and Fluorine-18 fluorodeoxyglucose (18F-FDG)
• Confirmation that study eligibility criteria have not been met between visits 1 and 2

Contacts and Locations

Contacts

Contact: Bijoy Kundu, PhD; (434) 924-0284; bkk5a@virginia.edu

Locations

United States, Virginia

University of Virginia; Recruiting

Charlottesville, Virginia, United States, 22903

Contact: Florence Yan 434-243-6768 fty5jf@hscmail.mcc.virginia.edu

Principal Investigator: Bijoy Kundu, PhD

Sponsors and Collaborators

University of Virginia

Investigators

• Principal Investigator: Bijoy Kundu, PhD; University of Virginia

More Information

• Responsible Party: Bijoy Kundu, Bijoy Kundu, PhD, University of Virginia
• ClinicalTrials.gov Identifier: NCT04315584
• Other Study ID Numbers: HSR190096
• First Posted: March 19, 2020
• Last Update Posted: March 24, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bijoy Kundu, University of Virginia:

glioblastoma; PET; CT; multiparametric MRI; brain imaging; tumor recurrence

Additional relevant MeSH terms:

Glioma; Glioblastoma; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Deoxyglucose; Fluorodeoxyglucose F18; Dihydroxyphenylalanine; Radiopharmaceuticals; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Antimetabolites; Antiviral Agents; Anti-Infective Agents; Dopamine Agents; Neurotransmitter Agents