18F-DOPA-PET in Finding Tumors in Patients With Newly Diagnosed Gliomas Undergoing Radiation Therapy

Evaluating the Impact of 18F-DOPA-PET on Radiotherapy Planning for Newly Diagnosed Gliomas

This phase II trial studies how well fluorine F 18 fluorodopa (18F-DOPA)-positron emission tomography (PET) works in finding tumors in patients with newly diagnosed gliomas undergoing radiation therapy. Comparing results of diagnostic procedures done before and during radiation therapy may help doctors predict a patient's response to treatment and help plan the best treatment.

Study Overview

• Status: Completed
• Conditions: Malignant Glioma
• Intervention / Treatment: Other: Quality-of-Life Assessment; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Diffusion Weighted Imaging; Procedure: Perfusion Magnetic Resonance Imaging; Drug: Fluorine F 18 Fluorodopa; Procedure: Positron Emission Tomography; Drug: Temozolomide

Detailed Description

PRIMARY OBJECTIVES:

I. Compare confirmed-progression free survival at 6 months for grade IV MGMT unmethylated glioma patients after radiation therapy targeting volumes designed with both 18F-DOPA PET and conventional magnetic resonance (MR) image information with historical controls from Mayo Clinic Rochester patients, including those treated on North Central Cancer Treatment Group (NCCTG) clinical trials.

SECONDARY OBJECTIVES:

I. Compare progression free survival at 12 months for grade III patients after radiation therapy targeting volumes designed with both 18F-DOPA PET and conventional MR image information with historical controls from Mayo Clinic Rochester patients, including those on NCCTG clinical trials.

II. Compare patient overall survival after radiation therapy targeting volumes designed with both 18F-DOPA PET and conventional MR image information with historical controls from Mayo Clinic Rochester patients, including those on NCCTG clinical trials.

III. Evaluate quality of life after radiotherapy treatment targeting dose escalated volumes defined to include high 18F-DOPA PET uptake.

IV. Determine acute and late effect toxicity after radiotherapy treatment targeting dose escalated volumes defined to include high 18F-DOPA PET uptake.

V. Compare confirmed-progression free survival at 12 months for grade IV MGMT methylated patients after radiation therapy targeting volumes designed with both 18F-DOPA PET and conventional MR image information with historical controls from Mayo Clinic Rochester patients, including those on NCCTG clinical trials.

VI. Compare confirmed-progression free survival in grade IV MGMT un-methylated patients with similar historical controls from Mayo Clinic Rochester patients, including those on NCCTG clinical trials.

VII. Compare confirmed-progression free survival in grade IV MGMT methylated patients with similar historical controls from Mayo Clinic Rochester patients, including those on NCCTG clinical trials.

TERTIARY OBJECTIVES:

I. Compare radiation therapy (RT) treatment volumes defined by MR only with RT treatment volumes defined with both PET and MR information for grade IV glioma patients.

II. Compare timing of accurate identification of progression defined by 18F-DOPA PET, perfusion magnetic resonance imaging (pMRI) and conventional MRI for grade IV glioma patients.

III. Compare patterns of failure after radiation therapy targeting volumes defined with target volumes designed to with both 18F-DOPA PET and conventional MR image information with patterns of failure for historical controls from Mayo Clinic Rochester patients, including those on NCCTG clinical trials.

IV. Compare RT treatment volumes defined by MR only with RT treatment volumes defined with both PET and MR information for grade III glioma patients.

V. Evaluate intra- and inter-observer variability with vs. without the addition of 18F-DOPA PET uptake for radiotherapy target volume delineation.

VI. Compare timing of accurate identification of progression defined by 18F-DOPA PET, pMRI and conventional MRI for grade III glioma patients.

VII. Compare predictive capabilities of 18F-DOPA PET, pMRI and diffusion tensor imaging (DTI) for localization of recurrences for patients treated with 18F-DOPA PET-guided RT dose escalation.

OUTLINE:

Patients undergo 18F DOPA-PET, pMRI, and DTI within 14 days before radiation therapy, 3-6 weeks after radiation therapy, and during follow-up. Patients also undergo intensity-modulated radiation therapy (IMRT) over 30 fractions and receive temozolomide.

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

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically confirmed newly diagnosed grade IV malignant glioma; Note: grade III patients are no longer being enrolled
• Computed tomography (CT) simulation, immobilization, MRI and PET imaging, treatment planning, and all follow-up MRI and PET scans to be performed at Mayo Clinic Rochester; Note: the actual radiation therapy treatments and follow-up other than imaging can be performed at Mayo Clinic Rochester, Northfield, LaCrosse, Mankato, Eau Claire, or Albert Lea
• Provide written informed consent
• Ability to complete questionnaire(s) by themselves or with assistance

Exclusion Criteria:

• Patients diagnosed with anaplastic oligodendroglioma
• 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 consist of: amoxapine, amphetamine, benztropine, bupropion, 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 (PET, pMRI, DTI, IMRT, temozolomide); Patients undergo 18F DOPA-PET, pMRI and DTI within 14 days before radiation therapy, 3-6 weeks after radiation therapy, and during follow-up. Patients also undergo IMRT over 30 fractions and receive temozolomide.

Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Radiation: Intensity-Modulated Radiation Therapy; Undergo IMRT; Other Names: IMRT; Intensity Modulated RT; Intensity-Modulated Radiotherapy; 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; Procedure: Perfusion Magnetic Resonance Imaging; Undergo pMRI; Other Names: magnetic resonance perfusion imaging; Drug: Fluorine F 18 Fluorodopa; Undergo 18F-DOPA-PET; Other Names: 18F-FDOPA; Procedure: Positron Emission Tomography; Undergo 18F-DOPA-PET; Other Names: Medical Imaging, Positron Emission Tomography; PET; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PET SCAN; Drug: Temozolomide; Receive temozolomide; Other Names: Temodar; SCH 52365; Temodal; Temcad; Methazolastone; RP-46161; Temomedac; CCRG-81045; Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-; M & B 39831; M and B 39831

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Grade IV MGMT Un-methylated Patients That Experience Confirmed-progression-free Survival at 6 Months (CPFS6)	The proportion of Grade IV MGMT un-methylated patients that experience confirmed-progression-free survival at 6 months (CPFS6). Progression is defined by any of the following: ≥25% increase in the sum of products of perpendicular diameters of enhancing lesions compared to the smallest tumor measurement obtained either at baseline or best response, on stable or increasing doses of corticosteroids; Significant increase in T2/FLAIR non-enhancing lesion on stable or increasing doses of corticosteroids compared to baseline scan or best response following initiation of therapy, not due to co-morbid events; Any new lesion; Clear clinical deterioration not attributable to other causes apart from the tumor or changes in corticosteroid dose.; Failure to return for evaluation due to death or deteriorating condition; Clear progression of non-measurable disease	Time from registration to the confirmed disease progression, assessed at 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	The median survival time and 95%CI will be estimated using the method of Kaplan-Meier.	Up to 5 years
Progression Free Survival	The median progression-free survival time and 95%CI will be estimated using the method of Kaplan-Meier.	Up to 5 years
Quality of Life Evaluated With the M. D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT) Questionnaire	The MDASI-BT consists of 28 questions. Twenty-two questions are related to severity of symptoms over the last 24 hours and are answered on a scale of 0-10 where 0=not present and10=as bad as you can imagine. The remaining 6 questions are related to how symptoms have interfered with daily life over the past 24 hours and are answered on a scale of 0-10 where 0=did not interfere and 10=interfered completely. Higher scores indicate greater severity of symptoms and greater interference with daily life. Analysis will include median change percent from baseline.	Up to 5 years
Number of Patients Experiencing Grade 3+ Treatment-related Toxicities	Adverse events graded using Common Terminology Criteria for Adverse Events version 4.0	Up to 5 years
Number of Patients Experiencing Grade 4+ Late Treatment-related Toxicities	Late treatment-related toxicities will be assessed using the Radiation Therapy Oncology Group (RTOG) European Organization for Research and the Treatment of Cancer (EORTC) toxicity criteria.	Up to 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inter-observer Variability With or Without the Addition of 18F-DOPA Positron Emission Tomography Uptake for Radiotherapy Target Volume Delineation	The concordance correlation coefficient will be used to measure agreement between volumes generated with each method, as well as to evaluate inter-observer variability, where variability associated with magnetic resonance imaging will serve as the standard for comparison.	Up to 5 years
Intra-observer Variability With or Without the Addition of 18F-DOPA Positron Emission Tomography Uptake for Radiotherapy Target Volume Delineation	The concordance correlation coefficient will be used to measure agreement between volumes generated with each method, as well as to evaluate inter-observer variability, where variability associated with magnetic resonance imaging will serve as the standard for comparison.	Up to 5 years
Magnetic Resonance Imaging-only Defined Volumes and the Volumes Defined With the Combination of Magnetic Resonance and Positron Emission Tomography Planning	Paired t-test statistical analysis will be performed to determine if any differences exist and the level of statistical significance between treatment volumes defined by magnetic resonance imaging only and treatment volumes defined with both positron emission tomography and magnetic resonance imaging information. The analysis of volumes from 72 grade IV patients will have 90% power to detect differences in volumes with an effect size of 0.39 using a paired t-test with a 0.05 two-sided significance level. Alternate metrics for comparison will also be assessed, including spatial overlap, distanc	Up to 5 years
Patterns of Failure After Radiation Therapy Targeting Volumes by 18F-DOPA Positron Emission Tomography and Conventional Magnetic Resonance Imaging	Chi-square tests of proportions will be used to test for differences in the proportions of patients with central, in-field, marginal, or distant failures between the patients on this study and historical controls.	Up to 5 years
Predictive Capabilities of 18F-DOPA Positron Emission Tomography, Perfusion Magnetic Resonance Imaging, and Diffusion Tensor Imaging for Localization of Recurrences	Compared by identifying the recurrence volume with each modality and correlating with identification of aggressive disease in the pre-radiation therapy planning images.	Up to 5 years
Radiation Therapy Treatment Volumes Defined by Magnetic Resonance Imaging Only and Defined With Both Positron Emission Tomography and Magnetic Resonance Imaging Information for Grade III Glioma Patients	Paired t-test statistical analysis will be performed to determine if any differences exist and the level of statistical significance between treatment volumes defined by magnetic resonance imaging only and treatment volumes defined with both positron emission tomography and magnetic resonance imaging information.	Up to 5 years
Radiation Therapy Treatment Volumes Defined by Magnetic Resonance Imaging Only or Defined With Both Positron Emission Tomography and Magnetic Resonance Imaging Information for Grade IV Glioma Patients	Paired t-test statistical analysis will be performed to determine if any differences exist and the level of statistical significance between treatment volumes defined by magnetic resonance imaging only and treatment volumes defined with both positron emission tomography and magnetic resonance imaging information. The analysis of volumes from 72 grade IV patients will have 90% power to detect differences in volumes with an effect size of 0.39 using a paired t-test with a 0.05 two-sided significance level. Alternate metrics for comparison will also be assessed, including spatial overlap, distan	Up to 5 years
Timing of Accurate Identification of Progression Defined by 18F- DOPA Positron Emission Tomography, Perfusion Magnetic Resonance Imaging and Conventional Magnetic Resonance Imaging for Grade IV Glioma Patients	The progression identification timing will be compared by calculating the percentage of time each modality was earlier than conventional magnetic resonance imaging. With a sample size of 72, if the observed percentage earlier than conventional magnetic resonance imaging is 30% for either modality, a two-sided 95% confidence interval for a single proportion using the large sample normal approximation will be +/- 10.6%. Progression identification timing will also be compared using Kaplan-Meier methods and paired t-tests to determine if differences exist between the modalities.	Up to 5 years
Timing of Accurate Identification of Progression Defined by 18F- DOPA Positron Emission Tomography, Perfusion Magnetic Resonance Imaging and Conventional Magnetic Resonance Imaging for Grade III Glioma Patients	Progression identification timing will be compared using Kaplan-Meier methods and paired t-tests to determine if differences exist between the modalities. An exploratory analysis of diffusion tensor imaging for detecting invasive non-enhancing tumor recurrence will also be performed.	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

General Publications

• Laack NN, Pafundi D, Anderson SK, Kaufmann T, Lowe V, Hunt C, Vogen D, Yan E, Sarkaria J, Brown P, Kizilbash S, Uhm J, Ruff M, Zakhary M, Zhang Y, Seaberg M, Wan Chan Tseung HS, Kabat B, Kemp B, Brinkmann D. Initial Results of a Phase 2 Trial of 18F-DOPA PET-Guided Dose-Escalated Radiation Therapy for Glioblastoma. Int J Radiat Oncol Biol Phys. 2021 Aug 1;110(5):1383-1395. doi: 10.1016/j.ijrobp.2021.03.032. Epub 2021 Mar 23.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2013
• Primary Completion (Actual): July 1, 2019
• Study Completion (Actual): July 15, 2024

Study Registration Dates

• First Submitted: November 18, 2013
• First Submitted That Met QC Criteria: November 18, 2013
• First Posted (Estimated): November 25, 2013

Study Record Updates

• Last Update Posted (Estimated): October 20, 2025
• Last Update Submitted That Met QC Criteria: October 3, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Investigative Techniques; Therapeutics; Azoles; Dacarbazine; Triazenes; Imidazoles; Chemistry Techniques, Analytical; Spectrum Analysis; Radiotherapy; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Temozolomide; Magnetic Resonance Spectroscopy; Radiotherapy, Intensity-Modulated; fluorodopa F 18
• Other Study ID Numbers: MC1374 (Other Identifier: Mayo Clinic); NCI-2013-02242 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 13-005106 (Other Identifier: Mayo Clinic Institutional Review Board)