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

Robert Bok, MD, PhD

Status and phase: Enrolling; Early Phase 1

Conditions: Adult Gliomas, Mixed

Treatments: Procedure: Magnetic Resonance Image (MRI); Drug: Hyperpolarized Carbon 13 Alpha-ketoglutarate (HP C13-aKG)

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05851378

NCI-2023-03744 (Registry Identifier)

5P01CA118816-12 (U.S. NIH Grant/Contract)

2P50CA097257 (U.S. NIH Grant/Contract)

22925

Details and patient eligibility

About

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.

Full description

PRIMARY OBJECTIVES:

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

OUTLINE:

Participants will be assigned to one of 2 cohorts:

COHORT 1: Participants with IDH mutant glioma for sequence development.

COHORT 2: Participants with recurrent IDH mutant glioma before receiving surgical resection.

This imaging study will involve one MR scan with the administration of HP 13C-aKG and will receive a follow-up phone call within 1-7 days post-study to assess for late adverse events.

Enrollment: 40 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

40 participants in 2 patient groups

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

Experimental group

Description:

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 group

Description:

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.