Simultaneous Multinuclear Metabolic MRI in Newly Diagnosed or Recurrent Glioma

Early Phase 1

Recruiting

• Conditions: Recurrent Glioma; Recurrent Malignant Glioma; Glioma; Malignant Glioma
• Interventions: Procedure: Biospecimen Collection; Procedure: Diagnostic Imaging; Procedure: Magnetic Resonance Imaging

• Registration Number: NCT05045027
• Lead Sponsor: Jonsson Comprehensive Cancer Center

Brief Summary

This clinical trial constructs and tests a novel multinuclear metabolic magnetic resonance imaging (MRI) sequence in patients with glioma (brain tumor) that is newly diagnosed or has come back (recurrent). This trial aims to develop new diagnostic imaging technology that may bridge gaps between early detection and diagnosis, prognosis, and treatment in brain cancer.

Detailed Description

PRIMARY OBJECTIVES:

I. Construct and test a novel multinuclear Na+-H+ metabolic MRI sequence with sensitivity to Sodium (Na+) concentration, Potential of Hydrogen (pH), and oxygen (O2).

II. Correlate Na+-, pH-, and O2-weighted MR image measurements with sodium-proton exchanger isoform-1 (NHE1) immunohistochemistry (IHC), bioenergetics, and gene expression using stereotactic image-guided biopsies from human brain tumors.

III. Quantify changes in Na+-, pH-, and O2-weighted MR images after neoadjuvant anti-PD-1 immunotherapy in recurrent glioblastoma (GBM) and explore associated changes in tumor biology.

OUTLINE:

AIM 1: Previous scan data from healthy subjects is collected and analyzed.

AIM 2: Patients undergo MRI. Patients also undergo collection of tissue samples for IHC analysis.

AIM 3: Patients undergo multinuclear metabolic imaging before and after immunotherapy and prior to surgical resection.

Study Timeline

• Study Start: 2021-09-01
• Study First Submitted: 2021-09-07
• Study First Submitted QC: 2021-09-07
• Study First Posted: 2021-09-16
• Status Verified: 2024-09
• Last Update Submitted: 2024-09-27
• Last Update Posted: 2024-10-01
• Primary Completion: 2026-09-10
• Study Completion: 2027-09-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• AIM 1: Healthy volunteers with no evidence of brain tumors or neurologic disease
• AIM 1: Age 18+
• AIM 2: Newly diagnosed or recurrent suspected or confirmed glioma (low or high grade)
• AIM 2: 10 IDH mutant and 10 IDH wild type gliomas
• AIM 2: Clinically indicated for resective surgery or biopsy
• AIM 2: Age 18+
• AIM 2: Tumor size > 1x1x1 cm (measurable)
• AIM 3: Recurrent glioma enrolled in an immunotherapy trial or clinically indicated to receive immunotherapy including anti-PD1
• AIM 3: Age 18+

Exclusion Criteria

• AIM 1: Cannot safely perform an MRI
• AIM 1: Age < 18
• AIM 2: Cannot safely perform an MRI or use of MRI contrast agents
• AIM 2: Age < 18
• AIM 3: Cannot safely perform an MRI or use of MRI contrast agents
• AIM 3: Age < 18

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Basic science (MRI, metabolic imaging, tissue collection)	Biospecimen Collection	AIM 1: Previous scan data from healthy subjects is collected and analyzed. AIM 2: Patients undergo MRI. Patients also undergo collection of tissue samples for IHC analysis. AIM 3: Patients undergo multinuclear metabolic imaging before and after immunotherapy and prior to surgical resection.
Basic science (MRI, metabolic imaging, tissue collection)	Diagnostic Imaging	AIM 1: Previous scan data from healthy subjects is collected and analyzed. AIM 2: Patients undergo MRI. Patients also undergo collection of tissue samples for IHC analysis. AIM 3: Patients undergo multinuclear metabolic imaging before and after immunotherapy and prior to surgical resection.
Basic science (MRI, metabolic imaging, tissue collection)	Magnetic Resonance Imaging	AIM 1: Previous scan data from healthy subjects is collected and analyzed. AIM 2: Patients undergo MRI. Patients also undergo collection of tissue samples for IHC analysis. AIM 3: Patients undergo multinuclear metabolic imaging before and after immunotherapy and prior to surgical resection.

Primary Outcome Measures

Name	Time	Method
Total sodium concentration	Up to 5 years	Will calculate NaT using standard methodology and normalize it to ocular Na+ concentration, a constant 135 mmol/l. Will then test whether healthy tissue has a coefficient of variance (COV) of \< 10% across all 20 subjects.
NHE1 expression	Up to 5 years	Will create a comprehensive map of genes/pathways and unique cell subsets associated with NHE1 expression.
Tumor metabolism	Up to 5 years	Will examine the correlation between baseline tumor metabolism and change in metabolism with respect to overall survival using Cox multivariable regression.

Trial Locations

Locations (1)

UCLA / Jonsson Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States