Spectroscopic MRI Guided Proton Therapy in Assessing Metabolic Change in Pediatric Patients With Brain Tumors

Spectroscopic MRI Guided Proton Therapy for Pediatric High-Grade Glioma (RAD4500)

This trial studies how well spectroscopic magnetic resonance imaging (MRI) guided proton therapy works in assessing metabolic change in pediatric patients with brain tumors. The non-invasive imaging, such as spectroscopic MRI may help to map the differences in tumor metabolism compared to healthy tissue without injection of any contrast agent.

Study Overview

• Status: Recruiting
• Conditions: Malignant Brain Glioma
• Intervention / Treatment: Procedure: Magnetic Resonance Spectroscopic Imaging; Device: Proton Therapy

Detailed Description

PRIMARY OBJECTIVES:

I. To obtain spectroscopic (s)MRI data from pediatric high grade glioma (HGG) patients before receiving standard of care radiation therapy (RT) and correlate baseline Cho/NAA ratios to recurrence patterns. (Cohort 1, observational) II. To assess the feasibility and safety of using sMRI to define proton therapy high dose (60Gy) target volumes for treatment delivery. (Cohort 2, intervention)

SECONDARY OBJECTIVES:

I. To evaluate how Cho/NAA defined radiation target volumes compare to standard of care radiation target volumes in size and resulting radiation delivery to adjacent normal tissue, by creating mock comparison RT plans for each patient.

II. To compare voxel-to-voxel changes in pre-treatment and post-treatment sMRI and evaluate as potential early predictor of tumor response/recurrence.

III. To evaluate sMRI as a tool in identifying pseudoprogression vs. true progression and correlate post-treatment sMRI metabolite ratios with histopathology if collected.

IV. To report patterns of failure in relationship to the RT field (local, marginal, or distant), progression-free survival (PFS) and overall survival (OS) among all patients.

V. To report patient reported outcomes of health related quality of life (QOL) during and after proton therapy for pediatric HGG.

VI. To build a longitudinal tracking database including clinical data, imaging, and genomic molecular profiling for pediatric HGG treatment.

OUTLINE:

Patients undergo sMRI prior to radiation therapy, at 1, 4, and 7 months after RT, and at the time of suspected recurrence.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bree Eaton, MD; Phone Number: 404-778-3473; Email: brupper@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University Hospital/Winship Cancer Institute
      • Principal Investigator: Bree R. Eaton, MD
      • Contact: Hillary Gaines; Email: hillary.gaines@emoryhealthcare.org
    • Atlanta, Georgia, United States, 30308
      • Recruiting
      • Emory Proton Therapy Center
      • Contact: Ardith R. DeShay; Phone Number: 404-251-0753; Email: adeshay@emory.edu
      • Principal Investigator: Bree R. Eaton, MD
    • Atlanta, Georgia, United States, 30322
      • Not yet recruiting
      • Children's Healthcare of Atlanta - Scottish Rite
      • Contact: Christina Lomba; Phone Number: 404-785-4803; Email: christina.lomba@choa.org
      • Principal Investigator: Bree R. Eaton

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pathologically diagnosed high-grade glioma (World Health Organization [WHO] grade 3-4). Patients with a radiographically diagnosed high-grade glioma may enroll prior to pathologic confirmation, but would be removed from study if pathology did not confirm the diagnosis of high-grade glioma.
• Primary tumor located within the supratentorial brain.
• Recommended to receive definitive radiation therapy.
• Able to receive MRI scans.
• Both males and females, and members of all races and ethnic groups are eligible for this trial.

Exclusion Criteria:

• Patients with pacemakers, non-titanium aneurysm clips, neurostimulators, cochlear implants, non-titanium metal in ocular structures, or other incompatible implants which makes MRI safety an issue are excluded.
• Patients that have any significant medical illnesses that in the investigator's opinion cannot be adequately tolerate MRI scan are excluded.
• Pathology demonstrated low-grade glioma or other benign or non-invasive brain tumor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diagnostic (sMRI); Patients undergo sMRI over less than 1 hour within 7 days prior to start of standard of care radiation therapy and at 10 weeks.	Procedure: Magnetic Resonance Spectroscopic Imaging; Undergo sMRI; Other Names: 1H- Nuclear Magnetic Resonance Spectroscopic Imaging; 1H-nuclear magnetic resonance spectroscopic imaging; Magnetic Resonance Spectroscopy; MRS; MRS Imaging; MRSI; Proton Magnetic Resonance Spectroscopic Imaging; Device: Proton Therapy; Target volume treatment; Other Names: Magnetic Resonance Spectroscopy; Spectroscopic MRI; Proton Radiation Therapy; sMRI imaging; 3D whole brain MR spectroscopic imaging sequence
Active Comparator: Group 2; Patients will undergo 3-4 sMRI scans at baseline prior to RT, 1 month, 4 months, and 7 months after RT, and/or at any time of suspected tumor recurrence.	Procedure: Magnetic Resonance Spectroscopic Imaging; Undergo sMRI; Other Names: 1H- Nuclear Magnetic Resonance Spectroscopic Imaging; 1H-nuclear magnetic resonance spectroscopic imaging; Magnetic Resonance Spectroscopy; MRS; MRS Imaging; MRSI; Proton Magnetic Resonance Spectroscopic Imaging; Device: Proton Therapy; Target volume treatment; Other Names: Magnetic Resonance Spectroscopy; Spectroscopic MRI; Proton Radiation Therapy; sMRI imaging; 3D whole brain MR spectroscopic imaging sequence

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cho/NAA ratios at baseline in tumor and in regions of tumor recurrence in patients receiving standard of care radiotherapy	The spatial relationship between baseline sMRI abnormalities and tumor recurrence will be reported and proportion of overlap will be quantified.	Through study completion, an average of 1 year
Incidence of adverse events	Toxicity will be defined according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.	Through study completion, an average of 1 year
Feasibility of using sMRI to define proton therapy high dose (60Gy) target volumes for treatment delivery	Will be estimated by the Kaplan-Meier Method.	From Baseline up to 3 years from treatment

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Bree R Eaton, MD, Emory University Hospital/Winship Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2018
• Primary Completion (Estimated): October 13, 2024
• Study Completion (Estimated): October 13, 2024

Study Registration Dates

• First Submitted: May 20, 2021
• First Submitted That Met QC Criteria: May 26, 2021
• First Posted (Actual): June 1, 2021

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: IRB00106849; P30CA138292 (U.S. NIH Grant/Contract); NCI-2018-02065 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); RAD4500-18 (Other Identifier: Emory University Hospital/Winship Cancer Institute)

Drug and device information, study documents

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