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.
Additional locations may be listed on ClinicalTrials.gov for NCT03952598.
Locations matching your search criteria
United States
Maryland
Bethesda
National Institutes of Health Clinical CenterStatus: Active
Contact: National Cancer Institute Referral Office
Phone: 888-624-1937
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. 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.
- Metabolic imaging, including proton magnetic resonance spectroscopy (MRS) and
hyperpolarized (HP) 13C-Pyruvate MRSI, can safely detect the in vivo metabolic
changes in humans.
- This clinical study will allow a longitudinal monitoring of participants with
IDH-mutant gliomas for detection of disease progression, which is associated with
metabolic alterations, provide an unprecedented opportunity for biopsy of the tumor
for diagnostic confirmation and interrogation of the mechanisms of HT and HMP, and
potentially providing a specific treatment approach for HMP which has been
refractory to conventional brain tumor treatments.
Objective:
To detect and monitor the quantitative levels of 2-HG and lactate/pyruvate ratio
longitudinally in participants with IDH-mutant gliomas via proton MRS and HP 13C pyruvate
MRSI, respectively
Eligibility:
- Participant has glioma harboring IDH1 or IDH2 mutation confirmed by DNA sequencing.
- Age >=18 years, KPS >= 70%
Design:
- This is a prospective observational study. We will recruit up to 270 eligible
participants in the next 5 years.
- The relationship between the occurrence of HT and the changes in 2-HG level and the
ratio of lactate/pyruvate will be evaluated using the proportional hazard model with
the latter as the time-dependent covariates.
Lead OrganizationNational Cancer Institute
Principal InvestigatorJing Wu
