Magnetic Resonance Imaging for Improving Knowledge of Brain Tumor Biology in Patients With Resectable Glioblastoma

• Sponsor: Jonsson Comprehensive Cancer Center (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT06090903
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 50
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 72.1
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This clinical trial uses a type of imaging scan called magnetic resonance imaging (MRI) to study brain tumor biology in patients with glioblastoma that can be removed by surgery (resectable). Malignant gliomas are the second leading cause of cancer mortality in people under the age of 35 in the United States. Glioblastoma is a type of malignant glioma with very poor patient prognosis. There are currently only about 3 drugs approved by the Food and Drug Administration (FDA) for the treatment of glioblastoma, one of them being administration of bevacizumab, which is very expensive. It is the most widely used treatment for glioblastoma with dramatic results. However, previous clinical trials have not demonstrated an overall survival benefit across all patient populations with glioblastoma that has returned after treatment (recurrent). The study aims to identify which patients who will benefit from bevacizumab therapy by observing MRI images and corresponding imaging biomarkers.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma; Recurrent Glioblastoma; Resectable Glioblastoma	Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Other: Medical Chart Review	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. Enhancing tumors with high diffusion measurements (low apparent diffusion coefficient [ADCL] > 1.24 um^{2/ms) will have higher DCN protein expression compared with tumors exhibiting low diffusion measurements (ADCL < 1.24 um}2/ms.) (Aim 1A) II. Enhancing tumors with high diffusion measurements (low apparent diffusion coefficient [ADCL] > 1.24 um^{2/ms) will have higher deoxyribonucleic acid (DNA) expression compared with tumors exhibiting low diffusion measurements (ADCL < 1.24 um}2/ms.) (Aim 1B) III. Enhancing tumors with high diffusion measurements (low apparent diffusion coefficient [ADCL] > 1.24 um^{2/ms) will have higher ribonucleic acid (RNA) expression compared with tumors exhibiting low diffusion measurements (ADCL < 1.24 um}2/ms.) (Aim 1C) IV. Mesenchymal-Like (MES-like) cells will have higher frequency of incidence of tumors with high diffusion measurements (ADCL > 1.24 um^2/ms) and higher overall DCN expression levels compared to other genotypes.

SECONDARY OBJECTIVE:

1. DCN immunohistochemistry (IHC), in-situ hybridization (ISH), and RNA expression within the tumor will be linearly correlated with continuous values of diffusion measurements (ADCL).

OUTLINE:

Patients undergo one MRI scan over approximately 1 hour prior to surgery.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Screening
• Official Title: Exploration Into the Association Between Decorin (DCN) Expression and MR Phenotypes in GBM
• Actual Study Start Date: Apr 14, 2022
• Anticipated Primary Completion Date: Apr 18, 2027
• Anticipated Study Completion Date: Apr 18, 2028

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Screening (MRI) Patients undergo one MRI scan over approximately 1 hour prior to surgery.

Procedure: Biospecimen Collection; patients will receive 1-3 image-guided biopsies within tumor tissue already designated for resection or removal.; Other Names: Biological Sample Collection Biospecimen Collected Specimen Collection ; Procedure: Magnetic Resonance Imaging; Undergo MRI scan; Other Names: Magnetic Resonance Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan NMR Imaging NMRI Nuclear Magnetic Resonance Imaging ; Other: Medical Chart Review; Review Medical Chart; Other Names: Chart Review

Outcome Measures

Primary Outcome Measures

1. Decorin (DCN) expression [Up to 5 years]

   Will use a two-sided t-test to compare DCN immunohistochemistry (IHC), in-situ hybridization (ISH), and ribonucleic acid (RNA) sequencing positivity between low apparent diffusion coefficient (ADCL) < 1.24 um^2/ms and ADCL > 1.24 um2/ms groups.

2. DCN expression correlated to ADCL [Up to 5 years]

   Will assess whether DCN IHC, ISH, and RNA expression within the tumor is linearly correlated with continuous values of ADCL. To test this, will examine Pearson's correlation coefficient (R^2) and test whether the slope of the linear regression line is significantly different from zero. After purification, will also quantify the particular genotype or cell states represented by tumor cells for each ADCL phenotype.

3. Incidence of tumors with high diffusion measurements among MES-like cells [Up to 5 years]

   Will assess whether MES-like cells have higher frequency of incidence of ADCL > 1.24 um^2/ms compared to other genotypes. To test this, will use a chi-squared goodness of fit test to assess the frequency of observations and an analysis of variance (ANOVA) to look at DCN protein, deoxyribonucleic acid (DNA), and RNA expression between genotypes.

4. DCN expression among Mesenchymal-Like (MES-like) cells [Up to 5 years]

   Will assess whether MES-like cells have higher overall DCN expression levels compared to other genotypes. To test this, will use a chi-squared goodness of fit test to assess the frequency of observations and an ANOVA to look at DCN protein, DNA, and RNA expression between genotypes.

Secondary Outcome Measures

1. DCN protein concentration in blood plasma [Up to 5 years]

   Will compare DCN protein concentration in blood plasma and use a two-sided t-test to compare DCN concentration between ADCL < 1.24 um^2/ms and ADCL > 1.24 um^2/ms cohorts. We will also test whether blood plasma concentrations of DCN are linearly correlated with tumor IHC levels using Pearson's correlation coefficient (R^2) and test whether the slope of the linear regression line is significantly different from zero.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients > 18 years of age

• Patients with newly diagnosed, suspected or recurrent glioblastoma (GBM) patients with enhancing tumors greater than 1.5 mL clinically indicated for surgical resection. Recurrent GBM must have occurred more than 3 months after the end of radiation therapy per Response Assessment in Neuro-Oncology Criteria (RANO) guidelines

Exclusion Criteria:

• Counterindication to magnetic resonance imaging (MRI) (Patient has a pacemaker or metal in the body)

• Patients < 18 years of age

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA / Jonsson Comprehensive Cancer Center	Los Angeles	California	United States	90095

Sponsors and Collaborators

• Jonsson Comprehensive Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Benjamin M Ellingson, UCLA / Jonsson Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jonsson Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT06090903
• Other Study ID Numbers: 21-002112; NCI-2022-03536; R01CA270027
• First Posted: Oct 19, 2023
• Last Update Posted: Oct 19, 2023
• Last Verified: Aug 1, 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Glioblastoma

Study Results

No Results Posted as of Oct 19, 2023