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

Primary Purpose

Malignant Glioma, Recurrent Brain Neoplasm

Status
Active
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Biopsy
Computed Tomography
Diffusion Weighted Imaging
Fluorine F 18 Fluorodopa
Laboratory Biomarker Analysis
Perfusion Magnetic Resonance Imaging
Positron Emission Tomography
Therapeutic Conventional Surgery
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Malignant Glioma

Eligibility Criteria

7 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Diagnostic (18F-DOPA-PET)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
Progression free survival
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.

Full Information

First Posted
December 19, 2013
Last Updated
June 26, 2023
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02020720
Brief Title
18F-DOPA-PET in Planning Surgery in Patients With Gliomas
Official Title
Evaluating the Impact of 18F-DOPA-PET on Neurosurgical Planning for Gliomas
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 22, 2014 (Actual)
Primary Completion Date
October 25, 2019 (Actual)
Study Completion Date
December 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Glioma, Recurrent Brain Neoplasm

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
72 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Diagnostic (18F-DOPA-PET)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Biopsy
Other Intervention Name(s)
Bx
Intervention Description
Undergo image-guided biopsy
Intervention Type
Procedure
Intervention Name(s)
Computed Tomography
Other Intervention Name(s)
CAT, CAT Scan, Computerized Axial Tomography, Computerized Tomography, CT, CT SCAN, tomography
Intervention Description
Undergo 18F-DOPA-PET/CT
Intervention Type
Procedure
Intervention Name(s)
Diffusion Weighted Imaging
Other Intervention Name(s)
Diffusion Weighted MRI, Diffusion-Weighted Magnetic Resonance Imaging, Diffusion-Weighted MR Imaging, Diffusion-Weighted MRI, DWI, DWI MRI, DWI-MRI, MR Diffusion-Weighted Imaging
Intervention Description
Undergo DTI
Intervention Type
Drug
Intervention Name(s)
Fluorine F 18 Fluorodopa
Other Intervention Name(s)
18F-FDOPA
Intervention Description
Undergo 18F-DOPA-PET/CT
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Procedure
Intervention Name(s)
Perfusion Magnetic Resonance Imaging
Other Intervention Name(s)
magnetic resonance perfusion imaging
Intervention Description
Undergo pMRI
Intervention Type
Procedure
Intervention Name(s)
Positron Emission Tomography
Other Intervention Name(s)
Medical Imaging, Positron Emission Tomography, PET, PET SCAN, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging
Intervention Description
Undergo 18F-DOPA-PET/CT
Intervention Type
Procedure
Intervention Name(s)
Therapeutic Conventional Surgery
Intervention Description
Undergo stereotactic craniotomy
Primary Outcome Measure Information:
Title
Ratios of maximum tumor standardized uptake value (SUVmax) normalized to mean SUV (SUVmean) of T/N
Description
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.
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Differences in volumes generated from biopsy-validated thresholds evaluated by 18F-DOPA-PET, pMRI, and DTI
Description
Paired t-test statistical analysis will be performed to determine if any differences exist and the level of statistical significance between volumes.
Time Frame
Up to 5 years
Title
Histologic grade of the specimen defined as HGG, LGG, or non-malignant brain tissue
Description
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.
Time Frame
Up to 5 years
Title
MRI contrast enhancement values
Description
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.
Time Frame
Up to 5 years
Title
Progression free survival
Time Frame
The time from study entry to progression, assessed up to 5 years
Title
Proportion of patients whose maximum 18F-DOPA uptake samples are in agreement with the final diagnostic grade
Description
Associated confidence intervals will be estimated based on dividing the number of patients whose samples agree by the total number of patients.
Time Frame
Up to 5 years
Other Pre-specified Outcome Measures:
Title
Accurate identification of the highest grade/highest density disease
Description
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.
Time Frame
Up to 5 years
Title
Accurate identification of tumor extent
Description
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.
Time Frame
Up to 5 years
Title
Role of metabolic imaging in neurosurgical resection planning
Description
Paired t-test analysis will be performed to determine the level of statistical significance between conventional MRI only and PET + MRI volumes.
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
7 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nadia Laack
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

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

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