- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03952598
Studying the Biology of IDH-mutant Gliomas Via Longitudinal Observation of 2-hydroxyglutarate (2-HG) Using MR Spectroscopy
Studying the Biology of IDH-mutant Gliomas Via Longitudinal Observation of 2-Hydroxyglutarate (2-HG) Using MR Spectroscopy
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.
Study Overview
Status
Intervention / Treatment
Detailed Description
Background:
- Glioma is the most common malignant brain tumor. Genes coding for isocitrate dehydrogenase (IDH), a metabolic enzyme, are frequently mutated in gliomas, particularly lower-grade gliomas (LGGs). IDH mutation causes a unique tumor biology, including the accumulation of 2-hydroxyglutarate (2-HG), an oncometabolite, which in turn causes genomic hypermethylation and tumorigenesis.
- Despite having a better prognosis compared to their IDH WT counterparts, IDH-mutant LGGs undergo a slow but unremitting higher-grade transformation (HT) and eventually become high grade gliomas (HGGs). A subset of patients with transformed HGGs develop a hypermutator phenotype (HMP), possibly related to previous treatment with alkylating agents and radiotherapy. The timeline for the development of HT and HMP is unpredictable and there is no known way to prevent them from happening, largely due to a lack of understanding their biological mechanisms and lack of a non-invasive approach for potential early detection.
- Proton magnetic resonance spectroscopy (MRS) of the brain can detect 2-HG in a tumor harboring IDH mutation. There has been an increased interest in using quantitative 2-HG by MRS as a biomarker for IDH-mutant gliomas. This clinical study will allow a longitudinal monitoring of quantitative 2-HG by MRS in patients with IDH-mutant gliomas. We hypothesize that a significant increase in 2HG level is correlated with HT and/or HMP. The change in 2-HG level in conjunction with evaluation of tumor cellularity and other metabolite markers such as choline, creatinine and N-acetyl aspartate (NAA) will likely to provide insights into metabolic alterations that may correlate with HT/HMP and potentially provide the predictive biomarker for early detection of HT.
Objective:
-To monitor the quantitative levels of 2-hydroxyglutarate (2-HG) longitudinally in patients with IDH-mutant gliomas via proton magnetic resonance spectroscopy (1H-MRS).
Eligibility:
- IDH 1 or 2 mutation confirmed by DNA sequencing.
- Age greater than or equal to18 years, KPS greater than or equal to 60%
Design:
- This is prospective observational study. We will recruit at least 250 eligible patients in the next 5 years.
- The relationship between the occurrence of HT and the changes in 2-HG level using the proportional hazard model.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: NCI NOB Referral Group
- Phone Number: (866) 251-9686
- Email: ncinobreferrals@mail.nih.gov
Study Contact Backup
- Name: Jing Wu, M.D.
- Phone Number: (240) 760-6036
- Email: jing.wu3@nih.gov
Study Locations
-
-
Maryland
-
Bethesda, Maryland, United States, 20892
- Recruiting
- National Institutes of Health Clinical Center
-
Contact:
- For more information at the NIH Clinical Center contact National Cancer Institute Referral Office
- Phone Number: 888-624-1937
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
- INCLUSION CRITERIA:
- Patients must have histologically confirmed glioma with IDH1 or IDH2 mutation confirmed by DNA sequencing.
- Patients must have grade II, III or IV glioma.
- Patients must have measurable disease.
- Age greater than or equal to18 years. Tumor biology of IDH-mutant gliomas are different in pediatric tumors. Therefore, children will be excluded from the study.
- Karnofsky performance greater than or equal to 60%.
Patients must have normal kidney function as defined below:
- creatinine within normal institutional limits OR
- creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients withcreatinine levels above institutional normal (Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl)).
- Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.
EXCLUSION CRITERIA:
- Subjects with any coexisting medical or psychiatric condition that is likely to interfere with study procedures and/or results (such as allergy to gadolinium contrast, metal implants and so on).
- Pregnant women 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 c ntrast, breastfeeding should be discontinued for 72 hours following study imaging.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 1/Arm 1
Monitoring of quantitative levels of 2-hydroxyglutarate (2-HG) via proton magnetic resonance spectroscopy (1H-MRS)
|
Research proton MRS (1H-MRS)followed by DW-MRI
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To monitor the quantitative levels of 2-hydroxyglutarate (2-HG) longitudinally in patients with IDH mutant gliomas via proton magnetic resonance spectroscopy (1H-MRS)
Time Frame: 5 years
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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...
Time Frame: at clinical disease recurrence
|
Usefulness of 2-HG detection and its correlation with high grade transformation and HMP
|
at clinical disease recurrence
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jing Wu, M.D., National Cancer Institute (NCI)
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 190096
- 19-C-0096
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Glioma
-
Children's Hospital of PhiladelphiaBlue Earth Diagnostics; Dragon Master FoundationNot yet recruitingGlioma | Low-grade Glioma | Glioma, Malignant | Low Grade Glioma of Brain | Glioma IntracranialUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI); Food and Drug Administration (FDA)Active, not recruitingRecurrent Glioblastoma | Recurrent Malignant Glioma | Refractory Malignant Glioma | Recurrent WHO Grade III Glioma | Recurrent WHO Grade II Glioma | Refractory Glioblastoma | Refractory WHO Grade II Glioma | Refractory WHO Grade III GliomaUnited States
-
Children's Hospital of PhiladelphiaBlue Earth Diagnostics, Inc; Dragon Master FoundationRecruitingGlioma | High Grade Glioma | Glioma, Malignant | Diffuse Glioma | Glioma IntracranialUnited States
-
ChimerixActive, not recruitingGlioblastoma | Diffuse Midline Glioma | H3 K27M Glioma | Thalamic Glioma | Infratentorial Glioma | Basal Ganglia GliomaUnited States
-
University of California, San FranciscoBeiGene USA, Inc.; Pacific Pediatric Neuro-Oncology ConsortiumRecruitingGlioblastoma | Malignant Glioma | Recurrent Glioblastoma | Recurrent WHO Grade III Glioma | WHO Grade III Glioma | IDH2 Gene Mutation | IDH1 Gene Mutation | Low Grade Glioma | Recurrent WHO Grade II Glioma | WHO Grade II GliomaUnited States
-
Beijing Tiantan HospitalDuke UniversityUnknownGlioblastoma | High Grade Glioma | Glioma, Malignant | Glioma of BrainstemChina
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingGlioblastoma | Malignant Glioma | WHO Grade III Glioma | Recurrent Glioma | Refractory GliomaUnited States
-
Hospital del Río HortegaCompletedGlioma | Glioblastoma | Low-grade Glioma | Glioma, Malignant | High-grade GliomaSpain
-
Sabine Mueller, MD, PhDPacific Pediatric Neuro-Oncology ConsortiumRecruitingGlioblastoma | Malignant Glioma | Recurrent Glioblastoma | Recurrent Malignant Glioma | Recurrent Grade III Glioma | Grade III GliomaUnited States, Australia, Israel, Switzerland
-
Institut de Recherches Internationales ServierActive, not recruitingRecurrent Glioma | Grade 2 Glioma | Residual GliomaUnited States, Canada, Spain, Italy, United Kingdom, Switzerland, Israel, Japan, Netherlands, Germany, France
Clinical Trials on 3T MRI scanner
-
University of MiamiRecruitingGlioma | Brain Tumor | Malignant Glioma | Primary Brain Tumor | Malignant Primary Brain TumorUnited States
-
University of MinnesotaCompleted
-
NYU Langone HealthNational Institutes of Health (NIH)Completed
-
Hospices Civils de LyonCompleted
-
Cedars-Sinai Medical CenterRecruitingCoronary Artery Disease | CancerUnited States
-
London Health Sciences CentreUniversity of Western Ontario, Canada; London Regional Cancer Program, CanadaTerminated
-
Charite University, Berlin, GermanyCompleted
-
Dana-Farber Cancer InstituteAMAG Pharmaceuticals, Inc.WithdrawnEsophageal Cancer
-
Dartmouth-Hitchcock Medical CenterCompletedRecurrent High Grade GliomasUnited States
-
Centre Hospitalier Universitaire DijonCompletedEndolymphatic HydropsFrance