Quantitative Assessment of Radiation-induced Neuroinflammation - A Proof of Principle Study

QARIN 1 is a study of [18F]DPA-714 Translocation Protein (TSPO) Positron Emission Tomography (PET) for longitudinal, quantitative assessment of brain neuroinflammation following whole brain radiation therapy. This TSPO PET, uses a radioactive tracer. An optional MRI (magnetic resonance imaging) will also be performed to monitor brain microstructure damages induced by neuroinflammation.

Primary Objectives

• Assessment of temporal and regional variability of uptake of translocator protein (TSPO) positron emission tomography (PET) tracer.
• Regional variability will be assessed in medial temporal lobe, frontal lobe, and in white matter
• Temporal variability will be assessed by scanning each subject four-times: at baseline (before or within 2 weeks of start of radiation therapy), before start of chemotherapy, at 1 year from the initiation of the radiation therapy, and at 1.5-2 years from the initiation of the radiation therapy
• Correlation of radiation dose in specific brain regions with radiation induced neuroinflammation as measured by uptake of TSPO PET tracer.

Exploratory Objectives

• Assessment of radiation-induced brain microstructure injuries (RIBMI) in specific brain regions (medial temporal lobe, frontal lobe, and in white matter) using advanced magnetic resonance imaging (MRI) techniques.
• Association of radiation dose with MRI measures of RIBMI in these specific brain regions.
• Association of PET measures of RIN with MRI measures of RIBMI.
• Association of PET measure of RIN and MRI measures of RIBMI in specific regions of interest (ROI) with specific domain of neuro-cognition. For example, to investigate whether PET measure of RIN and MRI measures of RIBMI in hippocampal ROI have strongest association with episodic memory; whether frontal lobe cortical ROI are associated with attention and executive function.
• Association of a novel MRI based technique for assessment of RIN with TSPO PET.
• Association of the PET and MRI measure of neuroinflammation within 2- years of completion of radiation with delayed cognitive outcome that will be measured at 3, 4 and 5 years from the completion of radiation

Study Overview

• Status: Recruiting
• Conditions: Brain Tumor; Medulloblastoma
• Intervention / Treatment: Drug: [18F]DPA714

Detailed Description

The participant will have 4 PET scans using a novel PET tracer that will help the investigators to quantify when and where in brain neuroinflammation happens following radiation therapy. The participant will receive the first PET scan either before your first dose of radiation therapy or within 2 weeks of the start of radiation therapy. The second PET scan will be obtained before starting chemotherapy. The third scan will be after 1 year of treatment.The final scan will be 1 and a half to 2 years after the start of treatment.The scan process will begin an hour or so after the participant has been given tracer by injection. The entire PET scan process lasts about 2 hours.

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Asim Bag, MD; Phone Number: 866-278-5833; Email: referralinfo@stjude.org

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • Recruiting
      • St.Jude Children's Research Hospital
      • Contact: Asim Bag, MD; Phone Number: 866-278-5833; Email: referralinfo@stjude.org
      • Principal Investigator: Asim Bag, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 39 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Participant is at least 8 years of age
• Participants with histologically confirmed medulloblastoma and are scheduled to receive 36 Gy craniospinal irradiation
• Participant and/or guardian can understand and is willing to sign a written informed consent document according to institutional guidelines
• Subjects have either have high-affinity or mixed-affinity TSPO binding sites as determined by the single-nucleotide polymorphism (SNP) rs6971 in the TSPO gene.

Exclusion Criteria:

• Participants with a large pseudomeningocele (>4 cm in size) at the surgical site, complications from ventricular access (evidenced by hemorrhage and/or enhancement along the catheter), large subdural effusion in the supra-tentorial compartment (>1 cm in the maximum transverse dimension). All of these are expected to induce inflammation.
• Female participants of childbearing age must not be lactating due to theoretical potential harm to the infant from exposure to radiation.
• Subjects with low-affinity TSPO binding sites as determined by the single-nucleotide polymorphism (SNP) rs6971 in the TSPO gene.
• Pregnant subjects.
• Patients needing sedation for the PET scans.

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: Participants; Participants who meet the eligibility criteria in the study will receive Translocation Protein (TSPO) Positron Emission Tomography (PET) for longitudinal, quantitative assessment of brain neuroinflammation following whole brain radiation therapy.	Drug: [18F]DPA714; Intravenous injection; Before or within 2 weeks of starting radiation therapy; Before starting chemotherapy; 1 year after the start of radiation therapy Timing cont.; 1.5 to 2 years after the start of radiation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SUVr	SUVr values for dorsolateral prefrontal cortex comparing baseline vs. follow up 1	follow up 1: up to 13 weeks after radiation therapy
SUVr	SUVr values for medial prefrontal cortex comparing baseline vs. follow up 1	follow up 1 : up to 13 weeks after radiation therapy
SUVr	SUVr values for hippocampus comparing baseline vs. follow up 1.	follow up 1 : up to 13 weeks after radiation therapy
SUVr	SUVr values for Corpus callosum comparing baseline vs. follow up 1.	follow up 1 : up to 13 weeks after radiation therapy
SUVr	SUVr values for corticospinal tract comparing baseline vs. follow up 1.	follow up 1 : up to 13 weeks after radiation therapy
SUVr	SUVr values for superior longitudinal fasciculus comparing baseline vs. follow up 1	follow up 1 : up to 13 weeks after radiation therapy
SUVr	SUVr values for dorsolateral prefrontal cortex comparing baseline vs. follow up 2.	follow up 2: up to 53 weeks after radiation therapy
SUVr	SUVr values for medial prefrontal cortex comparing baseline vs. follow up 2.	follow up 2: up to 53 weeks after radiation therapy
SUVr	SUVr values for hippocampus comparing baseline vs. follow up 2.	follow up 2: up to 53 weeks after radiation therapy
SUVr	SUVr values for Corpus callosum comparing baseline vs. follow up 2.	follow up 2: up to 53 weeks after radiation therapy
SUVr	SUVr values for corticospinal tract comparing baseline vs. follow up 2.	follow up 2: up to 53 weeks after radiation therapy
SUVr	SUVr values for superior longitudinal fasciculus comparing baseline vs. follow up 2.	follow up 2: up to 53 weeks after radiation therapy
SUVr	SUVr values for dorsolateral prefrontal cortex comparing baseline vs. follow up 3.	follow up 3: up to 2 years after radiation therapy
SUVr	SUVr values for medial prefrontal cortex comparing baseline vs. follow up 3.	follow up 3: up to 2 years after radiation therapy
SUVr	SUVr values for hippocampus comparing baseline vs. follow up 3.	follow up 3: up to 2 years after radiation therapy
SUVr	SUVr values for Corpus callosum comparing baseline vs. follow up 3	follow up 3: up to 2 years after radiation therapy
SUVr	SUVr values for corticospinal tract comparing baseline vs. follow up 3.	follow up 3: up to 2 years after radiation therapy
SUVr	SUVr values for superior longitudinal fasciculus comparing baseline vs. follow up 3.	follow up 3: up to 2 years after radiation therapy

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Investigators: Principal Investigator: Asim Bag, MD, St. Jude Children's Research Hospital

Publications and helpful links

Helpful Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2022
• Primary Completion (Estimated): October 26, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 5, 2021
• First Submitted That Met QC Criteria: November 9, 2021
• First Posted (Actual): November 22, 2021

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Inflammation; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Medulloblastoma; Neuroinflammatory Diseases
• Other Study ID Numbers: QARIN1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.
• IPD Sharing Time Frame: Data will be made available at the time of article publication.
• IPD Sharing Access Criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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