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Trial record 5 of 22 for:    Recruiting, Enrolling by invitation Studies | Interventional Studies | glioma | United States | First posted from 04/01/2019 to 07/31/2019

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

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ClinicalTrials.gov Identifier: NCT03952598
Recruitment Status : Recruiting
First Posted : May 16, 2019
Last Update Posted : October 21, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

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.


Condition or disease Intervention/treatment Phase
Glioma Gliomas High Grade Glioma Malignant Glioma Low Grade Glioma Device: 3T MRI scanner Not Applicable

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.

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Study Type : Interventional
Estimated Enrollment : 270 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Studying the Biology of IDH-mutant Gliomas Via Longitudinal Observation of 2-Hydroxyglutarate (2-HG) Using MR Spectroscopy
Actual Study Start Date : October 16, 2019
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : December 31, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 1/Arm 1
Monitoring of quantitative levels of 2-hydroxyglutarate (2- HG) via proton magnetic resonance spectroscopy (1H-MRS)
Device: 3T MRI scanner
Research proton MRS (lH-MRS)followed by DW-MRI




Primary Outcome Measures :
  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) [ 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03952598


Contacts
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Contact: Christine M Bryla, R.N. (240) 760-6007 brylacm@mail.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Jing Wu, M.D. National Cancer Institute (NCI)

Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03952598     History of Changes
Other Study ID Numbers: 190096
19-C-0096
First Posted: May 16, 2019    Key Record Dates
Last Update Posted: October 21, 2019
Last Verified: October 16, 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Imaging
Higher-Grade Transformation
Biomarker for Cancer
High Grade Gliomas
Additional relevant MeSH terms:
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Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue