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

NCT05851378 | Recruiting Early Phase 1 DMC FDA Drug

• 4 other identifiers: 22925NCI-2023-037445P01CA118816-122P50CA097257
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Adult Gliomas, Mixed

Keywords

Isocitrate Dehydrogenase Mutation

Outcome Measures

Primary Outcomes (9)

• 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)

Study Arms (2)

Cohort 1: Hyperpolarized Carbon-13 Alpha-ketoglutarate (HP 13C-aKG)

EXPERIMENTAL

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.

Cohort 2: Hyperpolarized Carbon-13 Alpha-ketoglutarate (HP 13C-aKG)

EXPERIMENTAL

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.

Interventions

Magnetic Resonance Image (MRI) PROCEDURE

Magnetic resonance imaging is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body

Also known as: MRI, MRI scan

Hyperpolarized Carbon 13 Alpha-ketoglutarate (HP C13-aKG) DRUG

Given intravenously at time of imaging

Also known as: Hyperpolarized C13-aKG, HP C13-aKG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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:
• Participants must have a life expectancy \> 8 weeks.
• Participants must have a Karnofsky performance status of \> 70.
• 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.
• 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.
• Participants must not have New York Heart Association (NYHA) Grade II or greater congestive heart failure.
• Participants must not have history of myocardial infarction or unstable angina within 12 months prior to study enrollment.
• 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.
• Participants may not be known to be HIV-positive. HIV testing is not required for study participation.
• 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.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Robert Bok, MD, PhD: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

MeSH Terms

Conditions

Glioma

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Susan Chang, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wendy Ma

CONTACT

(415) 514-4418; Wendy.Ma@ucsf.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Participating Investigator

Study Record Dates

• First Submitted: May 1, 2023
• First Posted: May 9, 2023
• Study Start: April 11, 2023
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2027
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)