Hyperpolarized Carbon-13 Alpha-ketoglutarate Imaging in IDH Mutant Glioma

Hyperpolarized Carbon-13 Alpha-ketoglutarate Metabolic Imaging in IDH Mutant Glioma

This study will investigate the use of hyperpolarized (HP) carbon-13 (13C) alpha-ketoglutarate (aKG) (HP 13C-aKG) to characterize tumor burden in patients with isocitrate dehydrogenase (IDH) mutant glioma.

Study Overview

• Status: Recruiting
• Conditions: Adult Gliomas, Mixed
• Intervention / Treatment: Drug: Hyperpolarized Carbon 13 Alpha-ketoglutarate (HP C13-aKG); Procedure: Magnetic Resonance Image (MRI)

Detailed Description

PRIMARY OBJECTIVES:

I. To define the most appropriate imaging parameters for obtaining hyperpolarized 13C-aKG from patients with IDH mutant glioma.

II. To assess the safety and feasibility of hyperpolarized 13C-aKG magnetic resonance (MR) metabolic imaging as a new and unique tool for evaluating tumor burden in patients with IDH mutant glioma.

OUTLINE:

This imaging study will involve one MR scan with the administration of HP 13C-aKG. Patients will be assigned to one of 2 cohorts: Cohort 1 (Participants with IDH mutant glioma for sequence development) and Cohort 2 (Participants with recurrent IDH mutant glioma before receiving surgical resection).

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Wendy Ma; Phone Number: (415) 514-4418; Email: Wendy.Ma@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco
      • Contact: Wendy Ma; Phone Number: 415-514-4418; Email: Wendy.Ma@ucsf.edu
      • Principal Investigator: Susan Chang, MD
      • Sub-Investigator: Daniel Vigneron, PhD
      • Contact: Phone Number: 877-827-3222; Email: cancertrials@ucsf.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants must be > 18 years old who have evidence of evaluable disease (with contrast enhancing lesion or non-enhancing lesion > 1 cubic centimetre (cc))

• Cohort 1: Participants with IDH mutant glioma who may or may not have received prior treatment
• Cohort 2: Participants with recurrent IDH mutant glioma before receiving surgical resection,

All the subjects must have prior MR scans available for review to assess the location and size of residual/recurrent tumor and do not have contraindication for magnetic resonance (MR) examinations. To be included in the study all subjects must also meet the following criteria:

1. Participants must have a life expectancy > 8 weeks.
2. Participants must have a Karnofsky performance status of > 70.
3. Participants must have adequate renal function (creatinine < 1.5 mg/dL). This test must be performed within 60 days prior to the HP 13C Imaging scan.
4. Participants must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy, would compromise the participant's ability to participate in this study or any disease that will obscure toxicity or dangerously impact response to the imaging agent.
5. Participants must not have New York Heart Association (NYHA) Grade II or greater congestive heart failure.
6. Participants must not have history of myocardial infarction or unstable angina within 12 months prior to study enrollment.
7. This study was designed to include women and minorities but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender. Minorities will actively be recruited to participate. No exclusion to this study will be based on race.
8. Participants must sign an informed consent indicating that they are aware of the investigational nature of this study. Participants must sign an authorization for the release of their protected health information.
9. Participants may not be known to be HIV-positive. HIV testing is not required for study participation.
10. Participants must not have a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless they are in complete remission and have been off all therapy for that disease for a minimum of 3 years.
11. Participants must not be pregnant or breast-feeding. Women of childbearing potential are required to obtain a negative pregnancy test within 14 days of Hyperpolarized Imaging scan. Effective contraception (men and women) must be used in subjects of childbearing potential.

Exclusion Criteria:

1. Participants are excluded from participating in this study if they are not able to comply with study procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Hyperpolarized Carbon-13 Alpha-ketoglutarate (HP 13C-aKG); Cohort 1 will be comprised of 10 participants with Isocitrate dehydrogenase (IDH) mutant glioma who may or may not have received prior treatment for optimizing imaging protocol. Participants will be injected with 0.67ml/kg actual body weight of 100 millimolar (mM) of α-KG solution and have a single imaging scan.	Drug: Hyperpolarized Carbon 13 Alpha-ketoglutarate (HP C13-aKG); Given intravenously at time of imaging; Other Names: Hyperpolarized C13-aKG; HP C13-aKG; Procedure: Magnetic Resonance Image (MRI); Magnetic resonance imaging is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body; Other Names: MRI; MRI scan
Experimental: Cohort 2: Hyperpolarized Carbon-13 Alpha-ketoglutarate (HP 13C-aKG); Cohort 2 will be comprised 30 participants with recurrent IDH mutant glioma before receiving surgical resection. Participants will be injected with 0.67ml/kg actual body weight of 100 millimolar (mM) of α-KG solution and have a single imaging scan.	Drug: Hyperpolarized Carbon 13 Alpha-ketoglutarate (HP C13-aKG); Given intravenously at time of imaging; Other Names: Hyperpolarized C13-aKG; HP C13-aKG; Procedure: Magnetic Resonance Image (MRI); Magnetic resonance imaging is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body; Other Names: MRI; MRI scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean signal to noise ratio of HP 13C-aKG	Signal-to-noise ratio (SNR) of HP 13C-aKG will be calculated voxel-by-voxel, and within each region of interest (ROI). The parameters considered will be the mean SNR, within these ROIs. Acquisition parameters will be optimized (such as spatial resolution) to have the highest metabolite SNR and metabolite contrast.	Day of imaging (1 day)
Mean signal to noise ratio of oncometabolite 2-hydroxyglutarate (2-HG)	Signal-to-noise ratio (SNR) of HP 13C akG 2HG will be calculated voxel-by-voxel, and within each ROI. The parameters considered will be the mean SNR, the number of voxels with SNR 2HG within the normal brain > 3.0, the number of voxels with SNR 2HG within the lesion > 3.0. Acquisition parameters will be optimized (such as spatial resolution) to have the highest metabolite SNR and metabolite contrast. (2HG production only in the IDH mutant tumors).	Day of imaging (1 day)
Mean signal to noise ratio of of glutamate	Signal-to-noise ratio (SNR) of 13C aKG glutamate will be calculated voxel-by-voxel, and within each region of interest. The parameters considered will be the number of voxels with SNR glutamate within the normal brain > 3.0, the number of voxels with SNR glutamate within the lesion > 3.0, Acquisition parameters will be optimized (such as spatial resolution) to have the highest metabolite SNR and metabolite contrast (reduced glutamate within the lesion compared to the normal brain).	Day of imaging (1 day)
Median signal to noise ratio of 2HG to aKG	Metabolite ratios (2HG/aKG) will be calculated voxel-by-voxel, and within each ROI. Median, maximum, and sum of ratios will be reported. Acquisition parameters will be optimized (such as spatial resolution) to have the highest metabolite SNR and metabolite contrast (2HG production only in the IDH mutant tumors within the lesion compared to the normal brain).	Day of imaging (1 day)
Mean signal to noise ratio of 2HG to glutamate	Metabolite ratios (2HG/glutamate) will be calculated voxel-by-voxel, and within each ROI. Median, maximum, and sum of ratios will be reported. Acquisition parameters will be optimized (such as spatial resolution) to have the highest metabolite SNR and metabolite contrast (2HG production only in the IDH mutant tumors and reduced glutamate within the lesion compared to the normal brain).	Day of imaging (1 day)
Proportion of participants who reported treatment-emergent adverse events	Occurrence of clinically significant changes in safety variables, including injection site, as defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be reported.	Day of imaging (1 day)
Comparison of HP 13C 2HG/aKG ratio with surgical results (Cohort 2)	In Cohort 2, the ratio of 13C (2HG/aKG will be compared within normal appearing brain versus a brain with visible lesions using a two-sided paired t-test or Wilcoxon signed rank test	Day of imaging (1 day)
Comparison of HP 13C 2HG/glutamate ratio with surgical results (Cohort 2)	In Cohort 2, the ratio of 13C 2HG/glutamate will be compared within a normal appearing brain versus a brain with visible lesions using a two-sided paired t-test or Wilcoxon signed rank test	Day of imaging (1 day)
Comparison of HP 13C glutamate/aKG ratio with surgical results (Cohort 2)	In Cohort 2, the ratio of 13C glutamate/aKG will be compared within a normal appearing brain versus a brain with visible lesions using a two-sided paired t-test or Wilcoxon signed rank test	Day of imaging (1 day)

Collaborators and Investigators

• Sponsor: Robert Bok, MD, PhD
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Susan Chang, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2023
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): April 30, 2026

Study Registration Dates

• First Submitted: May 1, 2023
• First Submitted That Met QC Criteria: May 1, 2023
• First Posted (Actual): May 9, 2023

Study Record Updates

• Last Update Posted (Actual): August 24, 2023
• Last Update Submitted That Met QC Criteria: August 22, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Isocitrate Dehydrogenase Mutation
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: 22925; 2P50CA097257 (U.S. NIH Grant/Contract); 5P01CA118816-12 (U.S. NIH Grant/Contract); NCI-2023-03744 (Registry Identifier: NCI Clinical Trials Reporting Program (CTRP))

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