18F-DOPA-PET in Planning Surgery in Patients with Gliomas

Evaluating the Impact of 18F-DOPA-PET on Neurosurgical Planning for Gliomas

This pilot clinical trial studies fluorine F 18 fluorodopa (18F-DOPA)-positron emission tomography (PET) in planning surgery in patients with gliomas. New imaging procedures, such as 18F-DOPA-PET scan, may help find gliomas and may help in planning surgery.

Study Overview

• Status: Completed
• Conditions: Malignant Glioma; Recurrent Brain Neoplasm
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Procedure: Biopsy; Procedure: Computed Tomography; Procedure: Diffusion Weighted Imaging; Drug: Fluorine F 18 Fluorodopa; Procedure: Perfusion Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Procedure: Therapeutic Conventional Surgery

Detailed Description

PRIMARY OBJECTIVES:

I. Accurately define a standardized 18F-DOPA PET tumor/normal tissue (T/N) threshold to delineate high grade gliomas (HGG) from low grade gliomas (LGG).

SECONDARY OBJECTIVES:

I. Determine correlation between 18F-DOPA PET activity, magnetic resonance imaging (MRI) contrast enhancement and high- or low-grade glioma biopsies.

II. Compare grade from maximum 18F-DOPA uptake samples for all resection patients against the final diagnostic grade, based on the highest grade component from all stereotactic and non-stereotactic samples acquired for open resection patients.

III. Compare volume differences between 18F-DOPA PET activity, MRI contrast enhancement, perfusion MRI (pMRI), and diffusion tensor imaging (DTI) for neurosurgical planning.

IV. Assess the time to progression for patients receiving resections and biopsies only.

TERTIARY OBJECTIVES:

I. Compare histopathology correlations with 18F-DOPA PET against correlations with perfusion MR imaging for accurate identification of the highest grade/highest density disease.

II. Compare histopathology correlations with 18F-DOPA PET against correlations with diffusion tensor imaging information for accurate identification of tumor extent.

III. Compare neurosurgical resection extent volume delineation with and without 18F-FDOPA-PET metabolic imaging information to determine role of metabolic imaging in neurosurgical resection planning.

OUTLINE:

Within 1 week of biopsy or resection, patients undergo 18F-DOPA PET/computed tomography (CT) scan and pMRI and DTI at baseline. Patients then undergo stereotactic craniotomy or image-guided biopsy.

After completion of study treatment, patients are followed up yearly for 5 years.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• MRI findings compatible with newly diagnosed or recurrent high- or low-grade malignant glioma
• Planned craniotomy and resection or biopsy
• Willing to sign release of information for any radiation and/or follow-up records
• Provide informed written consent if >= 18 years; if < 18 years, provide informed written assent and parent or legal guardian provide informed written consent
• Ability to provide tissue for mandatory correlative research component

Exclusion Criteria:

• Unable to undergo MRI scans with contrast (e.g. cardiac pacemaker, defibrillator, kidney failure)
• Unable to undergo an 18F-DOPA PET scan (e.g. Parkinson's disease, taking anti-dopaminergic, or dopamine agonist medication or less than 6 half-lives from discontinuance of dopamine agonists; NOTE: other potentially interfering drugs: amoxapine, amphetamine, benztropine, buproprion, buspirone, cocaine, mazindol, methamphetamine, methylphenidate, norephedrine, phentermine, phenylpropanolamine, selegiline, paroxetine, citalopram, and sertraline; if a patient is on any of these drugs, list which ones on the on-study form

• Any of the following:

  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception

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: Diagnostic (18F-DOPA-PET); Within 1 week of biopsy or resection, patients undergo 18F-DOPA PET/CT scan and pMRI and DTI at baseline. Patients then undergo stereotactic craniotomy or image-guided biopsy.

Other: Laboratory Biomarker Analysis; Correlative studies; Procedure: Biopsy; Undergo image-guided biopsy; Other Names: Bx; Procedure: Computed Tomography; Undergo 18F-DOPA-PET/CT; Other Names: CT; CAT; CAT Scan; Computerized Axial Tomography; Computerized Tomography; tomography; CT SCAN; Procedure: Diffusion Weighted Imaging; Undergo DTI; Other Names: DWI; Diffusion Weighted MRI; Diffusion-Weighted Magnetic Resonance Imaging; Diffusion-Weighted MR Imaging; Diffusion-Weighted MRI; DWI MRI; DWI-MRI; MR Diffusion-Weighted Imaging; Drug: Fluorine F 18 Fluorodopa; Undergo 18F-DOPA-PET/CT; Other Names: 18F-FDOPA; Procedure: Perfusion Magnetic Resonance Imaging; Undergo pMRI; Other Names: magnetic resonance perfusion imaging; Procedure: Positron Emission Tomography; Undergo 18F-DOPA-PET/CT; Other Names: Medical Imaging, Positron Emission Tomography; PET; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PET SCAN; Procedure: Therapeutic Conventional Surgery; Undergo stereotactic craniotomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratios of maximum tumor standardized uptake value (SUVmax) normalized to mean SUV (SUVmean) of T/N	To determine the optimal PET threshold for distinguishing HGG from LGG brain tissue, receiver operating characteristic (ROC) analysis and the Youden's index (sum of the sensitivity and specificity - 1) will be used. The Youden's index will be calculated for each possible T/N threshold. The final ROC area under the curve (AUC) value and confidence intervals will be estimated using ROC analysis methods for clustered continuous data as described by Obychowski.	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in volumes generated from biopsy-validated thresholds evaluated by 18F-DOPA-PET, pMRI, and DTI	Paired t-test statistical analysis will be performed to determine if any differences exist and the level of statistical significance between volumes.	Up to 5 years
Histologic grade of the specimen defined as HGG, LGG, or non-malignant brain tissue	The relationship between these T/N values, MRI contrast enhancement values, and the histologic grade of the specimen (HGG, LGG, or non-malignant brain tissue) will be determined using multivariate linear regression. These models will also include as appropriate the specimen cellularity and necrosis values.	Up to 5 years
MRI contrast enhancement values	The relationship between these T/N values, MRI contrast enhancement values, and the histologic grade of the specimen (HGG, LGG, or non-malignant brain tissue) will be determined using multivariate linear regression. These models will also include as appropriate the specimen cellularity and necrosis values.	Up to 5 years
Progression free survival		The time from study entry to progression, assessed up to 5 years
Proportion of patients whose maximum 18F-DOPA uptake samples are in agreement with the final diagnostic grade	Associated confidence intervals will be estimated based on dividing the number of patients whose samples agree by the total number of patients.	Up to 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accurate identification of the highest grade/highest density disease	Paired t-test statistical analysis will be used to evaluate differences in volumes identified using biopsy-validated thresholds as highly aggressive disease comparing 18F-DOPA uptake and relative cerebral blood volume from pMRI.	Up to 5 years
Accurate identification of tumor extent	Paired t-test statistical analysis will be used to evaluate differences in volumes identified using biopsy-validated thresholds as disease extent comparing 18F-DOPA PET and diffusion maps from DTI.	Up to 5 years
Role of metabolic imaging in neurosurgical resection planning	Paired t-test analysis will be performed to determine the level of statistical significance between conventional MRI only and PET + MRI volumes.	Up to 5 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Nadia N. Laack, M.D., Mayo Clinic in Rochester; Principal Investigator: Debra H. Brinkmann, Ph.D., Mayo Clinic in Rochester

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2014
• Primary Completion (Actual): October 25, 2019
• Study Completion (Actual): January 10, 2024

Study Registration Dates

• First Submitted: December 19, 2013
• First Submitted That Met QC Criteria: December 19, 2013
• First Posted (Estimated): December 25, 2013

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 21, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Central Nervous System Neoplasms; Glioma; Brain Neoplasms; Physiological Effects of Drugs; Protective Agents; Cariostatic Agents; Fluorides
• Other Study ID Numbers: MC1373 (Other Identifier: Mayo Clinic); NCI-2013-02373 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P50CA108961 (U.S. NIH Grant/Contract); 13-005102 (Other Identifier: Mayo Clinic Institutional Review Board); R01CA178200 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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