Multimodality MRI and Liquid Biopsy in GBM

Multimodality MRI for Quantification of Tumor-associated Macrophages and Prediction of Somatic Mutation Detectability in Cell-free DNA in Adult Patients With Glioblastoma

Patients with a new diagnosis of high-grade glioma based on MRI, who are considered surgical candidates determined by neurosurgeons or patients with recurrent glioblastoma with the initial diagnosis of glioblastoma (histologic or molecular proof) and recommended for clinically surgical resection may be eligible for this study. Subjects may participate in this study if they are at least 18 years of age.

Ferumoxytol-enhanced MRI will be used to quantify tumor-associated macrophages. This is a non-therapeutic trial in that imaging will not be used to direct treatment decisions.

The blood draw is being completed to evaluate cell-free circulating tumor DNA (cfDNA) and cell-free tumor DNA (ctDNA).

Study Overview

• Status: Withdrawn
• Conditions: Glioblastoma Multiforme; Brain Tumor, Recurrent; Brain Tumor, Primary; Brain Tumor, Adult: Glioblastoma
• Intervention / Treatment: Diagnostic test: Post Feraheme Infusion MRI

Detailed Description

This is a pilot study in subjects with a new diagnosis of high-grade glioma based on classic MRI appearance who are considered surgical candidates and patients with histologically proven diagnosis of glioblastoma (GB) who have completed chemoradiation and now have new contrast-enhancing lesions or lesions showing increased enhancement ( 25% increase) who are recommended for a clinical surgical resection. Subjects may participate in this study if they are at least 18 years of age, most participants will be receiving care at the clinical practices of the University of Pennsylvania. Subjects who come to the University of Pennsylvania for diagnosis and/or treatment of GB and who meet the study inclusion criteria may be approached by study personnel for recruitment into this study. Subjects will be approached about study participation regardless of race or ethnic background. Investigators anticipate enrolling up to 30 participants. Subjects who consent but do not complete the study imaging will be considered not evaluable and will be replaced. Accrual will likely occur over approximately 2 years. After undergoing screening assessments and verifying eligibility for study participation subjects will undergo a research ferumoxytol-enhanced MRI of the brain and blood draws for liquid biopsy.

• Study Type: Interventional
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participants will be ≥ 18 years of age
2. Patients with new diagnosis of high grade glioma based on MRI, who are considered surgical candidates determined by neurosurgeons or recurrent glioblastoma with the initial diagnosis of glioblastoma (histologic or molecular proof) and recommended for clinically surgical resection
3. Life expectancy of greater than 3 months in the opinion of an investigator or treating physician.
4. Karnofsky performance status ≥ 60

Exclusion Criteria:

1. Inability to tolerate imaging procedures in the opinion of an investigator or treating physician
2. Females who are pregnant or breast feeding at the time of screening will not be eligible for this study; pregnancy status will be confirmed verbally prior to participating in any study procedures.
3. Any current medical condition, illness, or disorder as assessed by medical record review and/or self-reported that is considered by a physician investigator to be a condition that could compromise participant safety or successful participation in the study
4. Contraindications to MRI or use of ferumoxytol or gadolinium contrast

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ferumoxytol Infused MRI; Ferumoxytol is an iron replacement product that is FDA approved to treat iron deficiency anemia in patients with chronic kidney disease (CKD). In this study, ferumoxytol is used to quantify tumor-associated macrophages. The infused dose would be 5mg/kg.	Diagnostic test: Post Feraheme Infusion MRI; All participants will receive a ferumoxtyol (Feraheme) infusion 20-28 hours prior to a head MRI. In addition, a blood draw for liquid biopsy targeted tissue sampling during surgery and special iron and macrophage staining on the tumor tissue.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Macrophage quantification status	Macrophage quantification status will be determined using histology methods based on biopsy sites and will be correlated with ferumoxytol-enhanced MRI.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cell free tumor DNA (ctDNA)	To determine the proportion of mutations identified by biopsy that are correctly identified in samples of plasma ctDNA for each subject, and to explore the potential of imaging measures to predict that proportion	2 years

Collaborators and Investigators

• Sponsor: Abramson Cancer Center of the University of Pennsylvania
• Investigators: Principal Investigator: Seyed Ali Nabavizadeh, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 1, 2022
• Primary Completion (ANTICIPATED): June 1, 2022
• Study Completion (ANTICIPATED): June 22, 2022

Study Registration Dates

• First Submitted: February 25, 2021
• First Submitted That Met QC Criteria: February 25, 2021
• First Posted (ACTUAL): March 2, 2021

Study Record Updates

• Last Update Posted (ACTUAL): September 16, 2022
• Last Update Submitted That Met QC Criteria: September 15, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms; Glioblastoma; Brain Neoplasms; Hematinics; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Ferrosoferric Oxide
• Other Study ID Numbers: 843601

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No