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

Glioblastoma Clinical Trial

Official title:

Exploration Into the Association Between Decorin (DCN) Expression and MR Phenotypes in GBM

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06090903
• Other study ID #: 21-002112
• Secondary ID: NCI-2022-03536R0
• Status: Recruiting
• Phase: N/A
• Start date: April 14, 2022
• Est. completion date: April 18, 2028

Study information

• Verified date: August 2023
• Source: Jonsson Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

PRIMARY OBJECTIVES:

I. 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:

I. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: April 18, 2028
• Est. primary completion date: April 18, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glioblastoma
• Recurrent Glioblastoma

Intervention

Procedure:
• Biospecimen Collection
patients will receive 1-3 image-guided biopsies within tumor tissue already designated for resection or removal.
• Magnetic Resonance Imaging
Undergo MRI scan

Other:
• Medical Chart Review
Review Medical Chart

Locations

Country	Name	City	State
United States	UCLA / Jonsson Comprehensive Cancer Center	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
Jonsson Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Decorin (DCN) expression	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.	Up to 5 years
Primary	DCN expression correlated to ADCL	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.	Up to 5 years
Primary	Incidence of tumors with high diffusion measurements among MES-like cells	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.	Up to 5 years
Primary	DCN expression among Mesenchymal-Like (MES-like) cells	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.	Up to 5 years
Secondary	DCN protein concentration in blood plasma	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.	Up to 5 years