MR Spectroscopy for Brain Tumor
Recruiting in Palo Alto (17 mi)
Overseen byJing Wu, M.D.
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Disqualifiers: Pregnancy, Hypertension, Heart failure, others
No Placebo Group
Prior Safety Data
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the treatment MRS and MRI scans of the brain, AG-881, for brain tumors?
MR spectroscopy (MRS) can help in identifying active and microscopic disease in brain tumors, which MRI alone might miss, and it can also differentiate between tumor types and assess treatment outcomes. This suggests that MRS, as part of the treatment, could improve the accuracy of diagnosing and monitoring brain tumors.
12345Is MR Spectroscopy safe for humans?
MR Spectroscopy (MRS) is generally considered safe as it is a non-invasive imaging technique similar to MRI (magnetic resonance imaging), which has been widely used in clinical settings for various conditions without significant safety concerns.
16789How does MR Spectroscopy differ from other treatments for brain tumors?
MR Spectroscopy is unique because it is a non-invasive imaging technique that analyzes the chemical composition of brain tumors, helping to distinguish between different types and grades of tumors. Unlike traditional treatments that focus on removing or shrinking tumors, MR Spectroscopy provides detailed metabolic information that can guide diagnosis and treatment planning.
310111213Eligibility Criteria
This trial is for adults with gliomas (a type of brain cancer) that have specific mutations called IDH1 or IDH2. Participants must be over 18, able to perform daily activities at a reasonable level, and have normal kidney function. Pregnant women and individuals with conditions that could affect the study are excluded.Inclusion Criteria
My kidney function is normal, based on creatinine levels or clearance.
I can care for myself but may need occasional help.
My glioma has an IDH1 or IDH2 mutation confirmed by a DNA test.
+4 more
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).
I am not pregnant and can stop breastfeeding for 72 hours for an MRI scan.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Initial Evaluation
Participants undergo neurological exam, MRS and MRI scans of the brain, and repeat screening tests
1-2 weeks
1 visit (in-person)
Longitudinal Monitoring
Participants have follow-up visits every 2-6 months for the rest of their life, including scans to monitor 2-HG levels
Ongoing
1 visit every 2-6 months (in-person)
Follow-up
Participants are monitored for safety and effectiveness after initial evaluation and during ongoing monitoring
5 years
Participant Groups
The study uses advanced MRI scans to monitor levels of a substance called 2-HG in the brains of patients with these gene mutations. The goal is to understand how this buildup relates to tumor aggressiveness and help design better diagnostic tests.
3Treatment groups
Experimental Treatment
Group I: 3/Arms 3Experimental Treatment2 Interventions
Monitoring of quantitative levels of 2-hydroxyglutarate (2-HG) via proton magnetic resonance spectroscopy (1H-MRS)
Group II: 2/Arm 2Experimental Treatment1 Intervention
Monitoring of quantitative levels of 2-hydroxyglutarate (2-HG) via proton magnetic resonance spectroscopy (1H-MRS) and HP 13C pyruvate MRSI
Group III: 1/Arm 1Experimental Treatment1 Intervention
Monitoring of quantitative levels of 2-hydroxyglutarate (2-HG) via proton magnetic resonance spectroscopy (1H-MRS) -- THIS ARM IS NOW CLOSED
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
MR-spectroscopy guided target delineation for high-grade gliomas. [2019]Functional/metabolic information provided by MR-spectroscopy (MRSI) suggests MRI may not be a reliable indicator of active and microscopic disease in malignant brain tumors. We assessed the impact MRSI might have on the target volumes used for radiation therapy treatment planning for high-grade gliomas.
[Usefulness of Cho/Cr ratio in proton MR spectroscopy for differentiating residual/recurrent glioma from non-neoplastic lesions]. [2022]We evaluated the clinical usefulness of the Cho/Cr ratio of proton MR spectroscopy(1H-MRS) to differentiate residual/recurrent glioma from non-neoplastic lesions.
Intracranial tumors in children: small single-voxel proton MR spectroscopy using short- and long-echo sequences. [2019]We report preliminary experience using single-voxel, proton MR spectroscopy (MRS) employing small voxels of interest, in combination with short and long echo-time protocols, for the assessment of primary intracranial tumors in children. We examined 23 children with primary intracranial tumors detected by MRI, and 32 controls with similar ages, using MRS on a 1.5 T system. Localized single-voxel (3.7 +/- 1.3 cc) proton spectra were obtained with short-echo (2,000/18), stimulated-echo (STEAM) and long-echo (2,000/270) spin-echo (PRESS) protocols. All spectra were evaluated qualitatively; 10 tumor and 19 control spectra were processed for peak area quantification. Small voxels of interest were able to account for tissue heterogeneity. Combined acquisition of short- and long-echo spectra increased the number of detectable metabolites. The solid portion of all tumors exhibited reduced N-acetyl-aspartate (NAA), strong contribution from cholines (Cho) and inositols or glycine, minimal presence of total creatine (tCr), enhanced broad mobile lipid resonances and accumulated lactate. Calculated selected metabolite ratios of Cho/tCr and Cho/NAA were substantially increased from control values. The cystic portions of the masses showed only lipid and lactate peaks.
Proton MR spectroscopy of intracranial tumours: in vivo and in vitro studies. [2019]Proton magnetic resonance spectroscopy (1H MRS) was used to investigate intracranial tumours in vitro and in vivo. Biopsy specimens were studied from 47 patients, 11 of whom were also examined in vivo. Analysis was based on the signals from N-acetylaspartate (NAA), phosphocreatine plus creatine (Cr), choline-containing compounds (Cho), alanine (Ala), and lactate. Biopsy data from 26 astrocytomas showed that the NAA/Cr ratio differs significantly in all grades from its value in normal white matter and that the Cho/Cr ratio differs significantly in grade IV tumours from its value in the other grades. Meningiomas have an unusually high Ala/Cr ratio. Spectra obtained in vivo are consistent with in vitro results from the same patients, and their lactate signal provides additional information about abnormal metabolism. We conclude that 1H MRS has a clear role in the diagnosis and biochemical assessment of intracranial tumours and in the evaluation and monitoring of therapy.
1H-MRS in vivo predicts the early treatment outcome of postoperative radiotherapy for malignant gliomas. [2019]To analyze prospectively the prognostic significance of 1H magnetic resonance spectroscopy (MRS) in vivo recorded from the tumor bed of patients after surgery for malignant glioma.
Changes in serial magnetic resonance spectroscopy predict outcome in high-grade glioma during and after postoperative radiotherapy. [2011]To determine any correlation between magnetic resonance spectroscopy (MRS) pattern of high-grade glioma before, during, and after radiotherapy (RT) with overall survival (OS) and progression-free survival (PFS).
Evaluating Magnetic Resonance Spectroscopy as a Tool for Monitoring Therapeutic Response of Whole Brain Radiotherapy in a Mouse Model for Breast-to-Brain Metastasis. [2020]Brain metastases are the most common intracranial tumor in adults and are associated with poor patient prognosis and median survival of only a few months. Treatment options for brain metastasis patients remain limited and largely depend on surgical resection, radio- and/or chemotherapy. The development and pre-clinical testing of novel therapeutic strategies require reliable experimental models and diagnostic tools that closely mimic technologies that are used in the clinic and reflect histopathological and biochemical changes that distinguish tumor progression from therapeutic response. In this study, we sought to test the applicability of magnetic resonance (MR) spectroscopy in combination with MR imaging to closely monitor therapeutic efficacy in a breast-to-brain metastasis model. Given the importance of radiotherapy as the standard of care for the majority of brain metastases patients, we chose to monitor the post-irradiation response by magnetic resonance spectroscopy (MRS) in combination with MR imaging (MRI) using a 7 Tesla small animal scanner. Radiation was applied as whole brain radiotherapy (WBRT) using the image-guided Small Animal Radiation Research Platform (SARRP). Here we describe alterations in different metabolites, including creatine and N-acetylaspartate, that are characteristic for brain metastases progression and lactate, which indicates hypoxia, while choline levels remained stable. Radiotherapy resulted in normalization of metabolite levels indicating tumor stasis or regression in response to treatment. Our data indicate that the use of MR spectroscopy in addition to MRI represents a valuable tool to closely monitor not only volumetrical but also metabolic changes during tumor progression and to evaluate therapeutic efficacy of intervention strategies. Adapting the analytical technology in brain metastasis models to those used in clinical settings will increase the translational significance of experimental evaluation and thus contribute to the advancement of pre-clinical assessment of novel therapeutic strategies to improve treatment options for brain metastases patients.
Phase II trial of radiosurgery to magnetic resonance spectroscopy-defined high-risk tumor volumes in patients with glioblastoma multiforme. [2022]To determine the efficacy of a Gamma Knife stereotactic radiosurgery (SRS) boost to areas of high risk determined by magnetic resonance spectroscopy (MRS) functional imaging in addition to standard radiotherapy for patients with glioblastoma (GBM).
In vivo 3-T MR spectroscopy in the distinction of recurrent glioma versus radiation effects: initial experience. [2022]To determine if 3-T magnetic resonance (MR) spectroscopy allows accurate distinction of recurrent tumor from radiation effects in patients with gliomas of grade II or higher.
Magnetic resonance spectroscopy in intracranial tumours of glial origin. [2019]To determine in vivo magnetic resonance spectroscopy (MRS) characteristics of intracranial glial tumours and to assess MRS reliability in glioma grading and discrimination between different histopathological types of tumours.
Non-invasive in vivo localized 1H spectroscopy of human astrocytoma implanted in rat brain: regional differences followed in time. [2019]Human astrocytoma cells were cultured and inoculated into the rat brain. From the pre-clinical to the terminal state, tumour growth was monitored by in vivo MR imaging and by localized water-suppressed 1H spectroscopy (0.12-0.15 cm3 volumes) and spectroscopic imaging (0.01 cm3 voxels) employing the ACE localization technique. The MR experiments were conducted completely non-invasively, leaving the scalp intact. Brain spectra were obtained, showing distinct resonances for more than five different brain metabolites; they were not contaminated with lipid signals because of the adequate localization. Tumour progression, monitored in a selected volume of interest, was reflected in the corresponding spectra by decreasing intensities for resonances of N-acetyl aspartate and (phospho)creatine and increasing intensities for resonances of choline compounds and lactate. From spectroscopic imaging experiments metabolic heterogeneity could be deduced within the tumorous region. At particular times during tumour development spectra were obtained greatly resembling localized 1H MR spectra obtained from patients with astrocytomas by the use of similar localization methods. This emphasizes the relevance of animal model study for the evaluation of MR spectroscopic investigations in human brain tumour diagnosis and therapy evaluation.
In vivo 1H NMR spectroscopy of an intracerebral glioma in the rat. [2019]High-resolution 1H surface coil NMR spectroscopy (MRS) was used to evaluate in vivo the cerebral metabolism changes in rat brain induced by a glial tumor growing in situ. Tumor cells (C6 glioma cells) were stereotaxically placed in the right hemisphere superficially. 1H MRS was performed using 5-mm surface coils implanted over the right hemisphere and the water was suppressed using a binomial sequence. As the intracerebral tumor size increased, there was a marked decrease in the N-acetyl aspartate level and an increase in the 1.3 ppm peak. Edition of this peak showed that lactate increased but lipids increased much more than lactate. Moreover the ratio between the choline-phosphocholine and creatine-phosphocreatine peaks changed. This study demonstrates that high-resolution surface coil 1H MRS can be used to monitor changes in metabolism associated with growth of an experimentally induced rat brain tumor in situ.
Spatially localized in vivo 1H magnetic resonance spectroscopy of an intracerebral rat glioma. [2019]Surface coil MRI combined with spatially localized spectroscopy was used to noninvasively detect 1H signals from metabolites within an intracerebral malignant glioma in rats. The MRS pulse sequence was based upon two-dimensional ISIS, which restricted 1H signals to a column-shaped volume, combined with one-dimensional spectroscopic imaging, which further resolved the signals into 8 or 16 slices along the major axis of the column. All experiments were executed with adiabatic pulses which induced uniform spin excitation despite the inhomogeneous radiofrequency field distribution produced by the surface coil transmitter. Surface coil MRI and MRS experiments were performed on phantom samples, normal rat brains, and rat brains harboring malignant gliomas. Spatially resolved in vivo 1H spectra of intracerebral gliomas revealed significantly decreased concentrations of N-acetyl-aspartate and creatine and increased lactic acid (or lipids) as compared to the contralateral hemisphere. These results demonstrate that metabolic abnormalities in intracerebral rat gliomas can be spatially resolved in a noninvasive manner using localized in vivo 1H MRS.