18F-DOPA-PET/MRI Scan in Imaging Elderly Patients With Newly Diagnosed Grade IV Malignant Glioma or Glioblastoma During Planning for a Short Course of Proton Beam Radiation Therapy

Phase II Study of Short Course Hypofractionated Proton Beam Therapy Incorporating 18F-DOPA-PET/MRI for Elderly Patients With Newly Diagnosed Glioblastoma

This phase II trial studies how well fluorodopa F 18-positron emission tomography/magnetic resonance imaging scan (18F-DOPA-PET/MRI) works in imaging elderly patients with newly diagnosed grade IV malignant glioma or glioblastoma during planning for a short course of proton beam radiation therapy. 18F-DOPA is a chemical tracer that highlights certain cells during imaging. PET scan, is a metabolic imaging technique which takes advantage of how tumor cells take up nutrients differently than normal tissue. MRI scans are used to guide radiation therapy for most brain tumors. Hypofractionated proton beam therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Using 18FDOPA-PET scans along with MRI scans may be able to provide the radiation doctor with information on tumor tissue versus normal, healthy tissue and may help the doctor more accurately plan the radiation treatment.

Study Overview

• Status: Completed
• Conditions: Glioblastoma; Malignant Glioma
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Other: Fluorodopa F 18; Procedure: Positron Emission Tomography; Radiation: Proton Beam Radiation Therapy; Drug: Temozolomide

Detailed Description

PRIMARY OBJECTIVE:

I. Compare overall survival at 12 months for grade IV glioma patients after radiation therapy targeting volumes designed with both 18F-DOPA-PET and conventional magnetic resonance (MR) image (or PET/computed tomography [CT]) information with historical controls.

SECONDARY OBJECTIVES:

I. Compare progression free survival at 12 months after radiation therapy targeting volumes designed with both 18F-DOPA-PET and conventional MR image information with historical controls.

II. Determine acute and late effect toxicity after hypofractionated proton beam radiotherapy treatment including areas of high 18F-DOPA-PET uptake (T/N > 2.0).

CORRELATIVE RESEARCH OBJECTIVES:

I. Compare radiotherapy (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 differences in RT volumes identified using biopsy-validated thresholds as highly aggressive disease comparing 18F-DOPA uptake and relative cerebral blood volume (relCBV) from perfusion MRI (pMRI) as well as differences in RT volumes identified using biopsy-validated thresholds as tumor extent comparing 18F-DOPA uptake and diffusion maps from diffusion tensor imaging (DTI) will be evaluated.

III. Evaluate quality of life after radiotherapy using European Organization for Research and Treatment of Cancer (EORTC) questionnaires compared with historical controls from Keim-Guibert et al.

IV. Compare differences in proton radiation planning utilizing radiobiologic modeling/evaluation techniques performed at Mayo Clinic Rochester to linear energy transfer distribution evaluation at Mayo Clinic Arizona.

OUTLINE:

Patients receive 18F-DOPA intravenously (IV) and undergo PET/MRI or PET/CT imaging scan. Patients then receive proton beam radiotherapy over 5 or 10 consecutive days excluding weekend and standard of care temozolomide on days 1-7 or 1-14. Beginning cycles 2, patients receive standard of care temozolomide on days 1-5. Cycles with temozolomide repeat every 28 days for up to 7 cycles in the in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for 1 year, and then periodically for up to 5 years.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed newly diagnosed grade IV malignant glioma
• Planned radiation treatments at Mayo Clinic Arizona or Mayo Clinic Rochester
• Willing to sign release of information for any radiation and/or follow-up records
• Provide informed written consent
• Patients with estimated glomerular filtration rate (eGFR) >= 60 mg/min/1.72 m^2
• Ability to complete questionnaire(s) by themselves or with assistance
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2

Exclusion Criteria:

• Patients diagnosed with grades I-III glioma
• Currently on Avastin at time of treatment
• 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

• Pregnant women, nursing women, or men or women of childbearing potential who are unwilling to employ adequate contraception.

  • NOTE: All women enrolled in this study will be age 65 or over, and at the determination of the principal investigator (PI), will not be of childbearing potential. If the radiology department requires a pregnancy test before administering the 18FDOPA injection, they may perform one per their standard of care

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: Treatment (18F-DOPA, PET/MRI, PET/CT, temozolomide); Patients receive 18F-DOPA IV and undergo PET/MRI or PET/CT imaging scan. Patients then receive proton beam radiotherapy over 5 or 10 consecutive days excluding weekend and standard of care temozolomide on days 1-7 or 1-14. Beginning cycles 2, patients receive standard of care temozolomide on days 1-5. Cycles with temozolomide repeat every 28 days for up to 7 cycles in the in the absence of disease progression or unacceptable toxicity.

Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Procedure: Computed Tomography; Undergo PET/CT; Other Names: CT; CAT; CAT Scan; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Procedure: Magnetic Resonance Imaging; Undergo PET/MRI; Other Names: MRI; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Other: Fluorodopa F 18; Given IV; Other Names: (18F)FDOPA; 18F-DOPA; 18F-FDOPA; 3-(2-Fluoro-(sup 18)F-4,5-dihydroxyphenyl)-L-alanine; 6-(18F)Fluoro-L-DOPA; Fluorine F 18 Fluorodopa; Fluorine-18-fluoro-L-DOPA; Fluorodopa (18F); FLUORODOPA F-18; L-6-(18F)Fluoro-DOPA; Procedure: Positron Emission Tomography; Undergo PET/CT or PET/MRI; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; Radiation: Proton Beam Radiation Therapy; Receive proton beam RT; Other Names: Proton Radiation Therapy; PBRT; Proton; Radiation, Proton Beam; Drug: Temozolomide; Drug; Other Names: Temodar; SCH 52365; Temodal; Temcad; Methazolastone; RP-46161; Temomedac; TMZ; 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
Overall Survival (OS)	The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated utilizing exact binomial methodology. The distribution of survival time will be estimated using the method of Kaplan-Meier (1958).	Time from registration to death due to any cause, assessed up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	The distribution of progression free survival times groups will be estimated using the method of Kaplan-Meier (1958).	Time from registration to the earliest date documenting disease progression, assessed up to 5 years
Progression Free Survival	The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated utilizing exact binomial methodology.	At 12 months after radiation therapy
Incidence of Adverse Events (AEs)	The rate of acute and late treatment-related toxicities for newly diagnosed high-grade glioma patients treated with fluorodopa F 18-positron emission tomography (18F-DOPA PET) image-guided hypofractionated proton beam therapy will be determined, with acute radiotherapy (RT) toxicities graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	Up to 5 years post treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiotherapy (RT) Treatment Volumes	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 (MR) only and treatment volumes defined with both positron emission tomography (PET) and MR information.	Up to 5 years post treatment
Quality of Life (QOL)	QOL surveys will be compared to data from historical controls. Quality of life will be assessed at baseline and at each magnetic resonance imaging (MRI) evaluation (up to 6 evaluations). QOL will be measured using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30.	Up to 5 years post treatment
Differences in Proton Radiation Planning	Paired t-test statistical analysis will be performed to determine if any differences exist and the level of statistical significance between proton plan metrics based off the two modeling/evaluation techniques.	Up to 5 years post treatment

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Sujay A Vora, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2019
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): November 26, 2023

Study Registration Dates

• First Submitted: December 14, 2018
• First Submitted That Met QC Criteria: December 14, 2018
• First Posted (Actual): December 19, 2018

Study Record Updates

• Last Update Posted (Estimated): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 8, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Glioma; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protective Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Dopamine Agents; Cariostatic Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Temozolomide; Fluorides; Levodopa
• Other Study ID Numbers: MC1774 (Other Identifier: Mayo Clinic in Arizona); NCI-2018-02800 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No