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

Primary Purpose

Adult Gliomas, Mixed

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Hyperpolarized Carbon 13 Alpha-ketoglutarate (HP C13-aKG)
Magnetic Resonance Image (MRI)
Sponsored by
Robert Bok, MD, PhD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Adult Gliomas, Mixed focused on measuring Isocitrate Dehydrogenase Mutation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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: 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. 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. 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. Exclusion Criteria: 1. Participants are excluded from participating in this study if they are not able to comply with study procedures.

Sites / Locations

  • University of California, San FranciscoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

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

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

Arm 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 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.

Outcomes

Primary Outcome Measures

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.
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).
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).
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).
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).
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.
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
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
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

Secondary Outcome Measures

Full Information

First Posted
May 1, 2023
Last Updated
August 22, 2023
Sponsor
Robert Bok, MD, PhD
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT05851378
Brief Title
Hyperpolarized Carbon-13 Alpha-ketoglutarate Imaging in IDH Mutant Glioma
Official Title
Hyperpolarized Carbon-13 Alpha-ketoglutarate Metabolic Imaging in IDH Mutant Glioma
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 11, 2023 (Actual)
Primary Completion Date
April 30, 2026 (Anticipated)
Study Completion Date
April 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Robert Bok, MD, PhD
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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 patients with isocitrate dehydrogenase (IDH) mutant glioma.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Gliomas, Mixed
Keywords
Isocitrate Dehydrogenase Mutation

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1: Hyperpolarized Carbon-13 Alpha-ketoglutarate (HP 13C-aKG)
Arm Type
Experimental
Arm 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.
Arm Title
Cohort 2: Hyperpolarized Carbon-13 Alpha-ketoglutarate (HP 13C-aKG)
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Hyperpolarized Carbon 13 Alpha-ketoglutarate (HP C13-aKG)
Other Intervention Name(s)
Hyperpolarized C13-aKG, HP C13-aKG
Intervention Description
Given intravenously at time of imaging
Intervention Type
Procedure
Intervention Name(s)
Magnetic Resonance Image (MRI)
Other Intervention Name(s)
MRI, MRI scan
Intervention Description
Magnetic resonance imaging is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body
Primary Outcome Measure Information:
Title
Mean signal to noise ratio of HP 13C-aKG
Description
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.
Time Frame
Day of imaging (1 day)
Title
Mean signal to noise ratio of oncometabolite 2-hydroxyglutarate (2-HG)
Description
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).
Time Frame
Day of imaging (1 day)
Title
Mean signal to noise ratio of of glutamate
Description
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).
Time Frame
Day of imaging (1 day)
Title
Median signal to noise ratio of 2HG to aKG
Description
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).
Time Frame
Day of imaging (1 day)
Title
Mean signal to noise ratio of 2HG to glutamate
Description
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).
Time Frame
Day of imaging (1 day)
Title
Proportion of participants who reported treatment-emergent adverse events
Description
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.
Time Frame
Day of imaging (1 day)
Title
Comparison of HP 13C 2HG/aKG ratio with surgical results (Cohort 2)
Description
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
Time Frame
Day of imaging (1 day)
Title
Comparison of HP 13C 2HG/glutamate ratio with surgical results (Cohort 2)
Description
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
Time Frame
Day of imaging (1 day)
Title
Comparison of HP 13C glutamate/aKG ratio with surgical results (Cohort 2)
Description
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
Time Frame
Day of imaging (1 day)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: 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. 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. 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. Exclusion Criteria: 1. Participants are excluded from participating in this study if they are not able to comply with study procedures.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wendy Ma
Phone
(415) 514-4418
Email
Wendy.Ma@ucsf.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susan Chang, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wendy Ma
Phone
415-514-4418
Email
Wendy.Ma@ucsf.edu
Phone
877-827-3222
Email
cancertrials@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Susan Chang, MD
First Name & Middle Initial & Last Name & Degree
Daniel Vigneron, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

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

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