Clinical trial NCT04315584: FDG and FDOPA PET Demonstration of Functional Brain Abnormalities
Official title: FDG and FDOPA PET Demonstration of Functional Brain Abnormalities
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Glioblastoma
Keywords: glioblastoma
PET
CT
multiparametric MRI
brain imaging
tumor recurrence
Lead sponsor: University of Virginia
Sponsor class: OTHER
First posted: 2020-03-19
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All 5 study subjects will undergo the same procedures.
Primary purpose: DIAGNOSTIC

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.

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.

Eligibility 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

Primary outcomes:
measure: Quantitative parametric maps indicating differences in rates of glucose and amino acid uptake (Ki) obtained from dynamic FDG and FDOPA scans respectively.
timeFrame: Up to 6 months
measure: Quantitative parametric maps indicating differences in details (d) components of the wavelet transform analysis, d6 and d8, based on established tumor feature criterions.
timeFrame: Up to 6 months
measure: Semi-quantitative standardize uptake value (SUV) parametric maps based on static PET scans (last 20 minutes of the dynamic PET scans).
timeFrame: Up to 6 months
measure: MRI brain metrics
timeFrame: Up to 6 months
measure: Surgical pathology or 3-6 month interval multidisciplinary clinical evaluation.
timeFrame: Up to 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: University of Virginia
name: Bijoy Kundu, PhD
role: PRINCIPAL_INVESTIGATOR
References: