Studying the Biology of IDH-mutant Gliomas Via Longitudinal Observation of 2-hydroxyglutarate (2-HG) Using MR Spectroscopy

NCT03952598 | Suspended Phase 2 FDA Drug

• 2 other identifiers: 19009619-C-0096
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Glioma is a type of brain cancer. Some of these tumors have gene mutations. These mutations can cause a substance called 2-HG to build up in the brain. This makes the tumors more aggressive. Researchers want to better understand 2-HG buildup in the brain. They hope this can help them design better ways to test for gliomas. Objective: To monitor the level of 2-HG in the brains of people with gliomas that have mutations in the IDH1 or IDH2 genes. Eligibility: People ages 18 and older with gliomas with mutations in the IDH1 or IDH2 genes Design: Participants will be screened with: Medical and cancer history Physical exam Reviews of their symptoms and ability to perform normal activities Blood and urine tests MRI scan Samples of their tumor from a past surgery Documentation of their diagnosis and mutation status Participants will have an initial evaluation. This will include repeats of screening tests. It will also include: Neurological exam MRS and MRI scans of the brain: Participants will lie on a table that slides into a metal cylinder. A coil or soft padding will be placed around their head. They will have a contrast agent injected into a vein. Pictures will be taken of the brain. Participants will have follow-up visits every 2-6 month for the rest of their life. Visits will include scans.

Conditions

Glioma; Gliomas; High Grade Glioma; Malignant Glioma; Low Grade Glioma

Keywords

Imaging; Higher-Grade Transformation; Biomarker for Cancer; High Grade Gliomas

Outcome Measures

Primary Outcomes (1)

• To monitor the quantitative levels of 2-hydroxyglutarate (2-HG) longitudinally in patients with IDH mutant gliomas via proton magnetic resonance spectroscopy (1H-MRS)

  Changes in the level of 2-HG correlate with the occurrence of higher-grade transformation (HT) and/or development of hypermutator phenotype (HMP) in patients with IDH-mutant gliomas

  5 years

Secondary Outcomes (1)

• Determine the utility of 2-HG detection by 1H-MRS to predict higher-grade transformation (HT) and hypermutator phenotype (HMP) by correlating the 2-HG level with pathological diagnosis and tumor mutational load of the tumor tissue at time of rec...

  at clinical disease recurrence

Study Arms (3)

1/Arm 1

EXPERIMENTAL

Monitoring of quantitative levels of 2-hydroxyglutarate (2-HG) via proton magnetic resonance spectroscopy (1H-MRS) -- THIS ARM IS NOW CLOSED

Device: 3T MRI scanner

2/Arm 2

EXPERIMENTAL

Monitoring of quantitative levels of 2-hydroxyglutarate (2-HG) via proton magnetic resonance spectroscopy (1H-MRS) and HP 13C pyruvate MRSI

Device: 3T MRI scanner

3/Arms 3

EXPERIMENTAL

Monitoring of quantitative levels of 2-hydroxyglutarate (2-HG) via proton magnetic resonance spectroscopy (1H-MRS)

Drug: HP 13C Pyruvate; Device: 3T MRI scanner

Interventions

HP 13C Pyruvate DRUG

Contrast agent used with magnetic resonance spectroscopic imaging (MRSI)

3/Arms 3

3T MRI scanner DEVICE

Research proton MRS (1H-MRS) followed by DW-MRI

1/Arm 1; 2/Arm 2; 3/Arms 3

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically confirmed diffuse glioma with documented IDH1 or IDH2 mutation, confirmed by DNA sequencing the exception will be participants with brain lesions that are not safe for biopsy but clinically suspected to be diffuse glioma are allowed to enroll to the study to receive imaging study as part of the exploratory study
• Participants must have measurable disease.
• Age \>=18 years. Tumor biology of IDH-mutant gliomas are different in pediatric tumors. Therefore, children will be excluded from the study.
• Karnofsky performance \>= 70%.
• Participants must have documented normal kidney function as defined below:
• Creatinine within normal institutional limits
• Creatinine clearance \>60 mL/min/1.73 m2 for Participants with creatinine levels above institutional normal (Measured or calculated creatinine clearance
• Participants must have adequate liver function as defined below:
• total bilirubin \<=2x ULN (ULN 1.3 mg/dl) except for participants with Gilbert Syndrome
• AST \< 3x ULN (ULN 34U/L)
• ALT \< 3x ULN (ULN 55U/L)
• Ability of participants to understand and the willingness to sign a written informed consent document indicating that they are aware of the investigational nature of this study, and that this is not a therapeutic clinical trial.

You may not qualify if:

• Participants who have contraindication to MRI examination, including, but not limited to, unable to receive gadolinium, medical instability, or any contraindication on MR Screening Form. Pregnant individuals are excluded because MRI contrast, planned to be used on this study, may be dangerous for the fetus. Because there is an unknown but potential risk for adverse events in nursing infants secondary to using of MRI contrast, breastfeeding should be discontinued for 72 hours following study imaging.
• Participants weighing \> 350 lbs. (weight limit for scanner table), or unable to fit within the imaging gantry
• Poorly controlled hypertension, with blood pressure \>150/90 mmHg.
• Congestive heart failure with New York Heart Association (NYHA) status \> 2.
• A medical history of clinically significant EKG abnormalities, including QT prolongation, a family history of prolonged QT interval syndrome, or myocardial infarction (MI) less than 1 year ago with ensuing unstable EKG.
• Ongoing acute or chronic pulmonary bronchospastic disease, including a history of chronic obstructive pulmonary disease or asthma with an exacerbation within the past year.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Glioma

Condition Hierarchy (Ancestors)

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

Study Officials

• Jing Wu, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2019
• First Posted: May 16, 2019
• Study Start: October 16, 2019
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 14, 2026

Record last verified: 2026-01-21

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: BTRIS: Clinical data available during the study and indefinitely.@@@@@@dbGaP: Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: BTRIS: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.@@@@@@dbGaP: Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (1)