MR Spectroscopy for Brain Tumor

Overseen By Jing Wu, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Disqualifiers: Pregnancy, Hypertension, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

270 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand gliomas, a type of brain cancer, by monitoring a substance called 2-HG that accumulates in the brain when certain gene mutations are present. Researchers use advanced imaging techniques, such as MR spectroscopy (MRS) and MRI scans, to track these changes, potentially leading to better testing methods for these tumors. The trial seeks participants with gliomas that have specific gene mutations (IDH1 or IDH2) and symptoms affecting their daily lives. As a Phase 2 trial, it focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in glioma testing.

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 prior data suggests that MR Spectroscopy is safe for monitoring brain tumors?

Research has shown that proton magnetic resonance spectroscopy (MRS) is very safe. It doesn't use harmful radiation or require a dye injection, enhancing its safety profile. Studies have found that MRS is a noninvasive method, meaning it doesn't involve entering the body, and it can safely analyze body chemistry.

For the HP 13C pyruvate magnetic resonance spectroscopic imaging (MRSI) component, past studies have demonstrated its safety and feasibility. In one study, 31 men with prostate cancer underwent this procedure without any problems, suggesting it is well-tolerated and doesn't cause major side effects.

Overall, both techniques used in the trial have a strong safety record based on previous research. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these MRI and MRS techniques for brain tumors because they offer a non-invasive way to monitor the levels of 2-hydroxyglutarate (2-HG), a potential marker of tumor activity. Unlike traditional imaging methods that primarily show the tumor's size and shape, these advanced scans delve into the metabolic processes of the tumor. The proton magnetic resonance spectroscopy (1H-MRS) and the cutting-edge HP 13C pyruvate MRSI could provide earlier and more precise insights into how a tumor is behaving, possibly leading to more tailored treatment plans. This could mean faster adjustments in therapy, potentially improving patient outcomes.

What evidence suggests that this trial's methods could be effective for monitoring 2-HG in gliomas?

Research has shown that proton magnetic resonance spectroscopy (MRS) can effectively monitor levels of 2-hydroxyglutarate (2-HG) in brain tumors. High levels of 2-HG are linked to more aggressive brain tumors known as gliomas. In this trial, researchers will monitor participants using different MRS techniques. One group will use proton magnetic resonance spectroscopy (1H-MRS) alone, while another will use hyperpolarized 13C MRSI in addition to 1H-MRS. Studies have demonstrated that MRS can detect changes in the metabolism of brain tumors, aiding in understanding tumor behavior. These findings suggest that MRS could be a valuable tool for understanding and managing gliomas with certain genetic mutations. ^{2 6 7 8 9}

Who Is on the Research Team?

Jing Wu, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• MRS and MRI scans of the brain

Trial Overview 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.

How Is the Trial Designed?

Group I: 3/Arms 3 Experimental Treatment 2 Interventions

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

Group II: 2/Arm 2 Experimental Treatment 1 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 1 Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 34 patients with high-grade gliomas, MRSI revealed that metabolically active tumor regions often extended beyond what was identified by traditional MRI, indicating that MRI may underestimate the extent of active disease.

Incorporating MRSI into radiation therapy planning could lead to more accurate target volumes, potentially improving treatment effectiveness while minimizing unnecessary radiation exposure to healthy tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MR-spectroscopy guided target delineation for high-grade gliomas. Pirzkall, A., McKnight, TR., Graves, EE., et al.[2019]

The study successfully monitored tumor growth in rat brains using non-invasive MR imaging and localized 1H spectroscopy, allowing for detailed analysis of brain metabolites without damaging the scalp.

Changes in metabolite levels, such as decreased N-acetyl aspartate and increased choline compounds and lactate, were linked to tumor progression, highlighting the potential of this method for evaluating brain tumor development and treatment in both animal models and humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive in vivo localized 1H spectroscopy of human astrocytoma implanted in rat brain: regional differences followed in time. van Vaals, JJ., Bergman, AH., van den Boogert, HJ., et al.[2019]

Magnetic resonance spectroscopy (MRS) can effectively differentiate between WHO grade I and II astrocytomas and identify oligodendrogliomas, but it is not reliable for grading gliomas overall.

The study analyzed spectra from 39 patients with various types of gliomas and found significant differences in metabolite ratios compared to healthy controls, indicating distinct metabolic profiles for different tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance spectroscopy in intracranial tumours of glial origin. Jaskólski, DJ., Fortuniak, J., Majos, A., et al.[2019]

In a study of 23 children with primary intracranial tumors, single-voxel proton MR spectroscopy effectively identified metabolic changes, such as reduced N-acetyl-aspartate (NAA) and increased choline (Cho) levels, indicating tumor presence and characteristics.

The combination of short and long echo-time protocols enhanced the detection of various metabolites, allowing for a more comprehensive assessment of tumor heterogeneity and composition, which could aid in diagnosis and treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial tumors in children: small single-voxel proton MR spectroscopy using short- and long-echo sequences. Tzika, AA., Vigneron, DB., Dunn, RS., et al.[2019]

This study demonstrates that magnetic resonance (MR) spectroscopy combined with MR imaging can effectively monitor metabolic changes in a breast-to-brain metastasis model, providing insights into tumor progression and treatment response.

After applying whole brain radiotherapy, the study found that metabolite levels normalized, indicating tumor stasis or regression, which suggests that this imaging technique could be a valuable tool for evaluating the efficacy of new therapeutic strategies in brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating Magnetic Resonance Spectroscopy as a Tool for Monitoring Therapeutic Response of Whole Brain Radiotherapy in a Mouse Model for Breast-to-Brain Metastasis. Chae, WH., Niesel, K., Schulz, M., et al.[2020]

1H magnetic resonance spectroscopy (MRS) can provide important prognostic information for patients with malignant glioma after surgery, revealing significant changes in metabolic ratios that correlate with survival outcomes.

Specifically, a high lactate/N-acetyl aspartate (NAA) ratio (>2.0) is associated with a poor prognosis, showing only a 20% one-year survival rate, while a lower ratio (<2.0) indicates a much better prognosis with an 85% one-year survival rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

1H-MRS in vivo predicts the early treatment outcome of postoperative radiotherapy for malignant gliomas. Tarnawski, R., Sokol, M., Pieniazek, P., et al.[2019]

The Cho/Cr ratio measured by proton MR spectroscopy (1H-MRS) is effective in distinguishing between residual/recurrent gliomas and non-neoplastic lesions, with significantly higher ratios found in glioma cases (mean 1.70) compared to non-neoplastic lesions (mean 1.04).

Using a Cho/Cr ratio threshold of 1.5, the method demonstrated a sensitivity of 64%, specificity of 83%, and overall accuracy of 70%, indicating its potential as a useful diagnostic tool alongside traditional MRI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Usefulness of Cho/Cr ratio in proton MR spectroscopy for differentiating residual/recurrent glioma from non-neoplastic lesions]. Ando, K., Ishikura, R., Nagami, Y., et al.[2022]

Proton magnetic resonance spectroscopy (1H MRS) effectively differentiates between various grades of astrocytomas and meningiomas by analyzing specific metabolite ratios, such as NAA/Cr and Ala/Cr, in biopsy specimens from 47 patients.

The in vivo spectra obtained from 11 patients correlated well with in vitro biopsy results, indicating that 1H MRS can be a valuable tool for diagnosing and monitoring the biochemical status of intracranial tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton MR spectroscopy of intracranial tumours: in vivo and in vitro studies. Gill, SS., Thomas, DG., Van Bruggen, N., et al.[2019]

High-resolution 1H MRS spectroscopy effectively monitors metabolic changes in the rat brain as a glial tumor grows, showing a decrease in N-acetyl aspartate and significant increases in lactate and lipids.

The study highlights that the metabolic profile changes, including altered ratios of choline to creatine, can provide insights into tumor progression and brain metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo 1H NMR spectroscopy of an intracerebral glioma in the rat. Remy, C., Von Kienlin, M., Lotito, S., et al.[2019]

In a Phase II trial involving 35 patients with glioblastoma, the use of Gamma Knife stereotactic radiosurgery (SRS) targeting high-risk areas identified by magnetic resonance spectroscopy (MRS) resulted in a median survival of 15.8 months, which is significantly better than historical controls for similar treatments.

Patients receiving concurrent temozolomide along with the MRS-targeted SRS and standard radiotherapy had an even better median survival of 20.8 months, indicating that this combined approach may enhance treatment efficacy with manageable toxicity levels (11% experiencing grade 3/4 toxicities).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of radiosurgery to magnetic resonance spectroscopy-defined high-risk tumor volumes in patients with glioblastoma multiforme. Einstein, DB., Wessels, B., Bangert, B., et al.[2022]

Using surface coil MRI combined with localized spectroscopy, researchers successfully detected metabolic changes in malignant gliomas in rats, highlighting a noninvasive method to study brain tumors.

The study found significant decreases in N-acetyl-aspartate and creatine levels, along with increased lactic acid or lipids in gliomas compared to normal brain tissue, indicating distinct metabolic abnormalities associated with these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spatially localized in vivo 1H magnetic resonance spectroscopy of an intracerebral rat glioma. Ross, BD., Merkle, H., Hendrich, K., et al.[2019]

In a study of 26 patients with high-grade glioma undergoing radiotherapy, significant decreases in tumor metabolite ratios, particularly choline/N-acetyl-aspartate, were observed after treatment, indicating a potential response to therapy.

A greater than 40% decrease in normalized choline levels from week 4 of radiotherapy to 2 months post-treatment was associated with significantly worse overall survival (9.1 months) and progression-free survival (5.8 months), suggesting that monitoring these metabolite changes could help tailor more effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in serial magnetic resonance spectroscopy predict outcome in high-grade glioma during and after postoperative radiotherapy. Quon, H., Brunet, B., Alexander, A., et al.[2011]

In a study of 14 patients with gliomas who had previously received high-dose radiation, 3-T magnetic resonance spectroscopy was able to accurately distinguish between recurrent tumors and radiation effects in 16 out of 17 biopsy locations based on choline to creatine ratios.

The results showed that a higher choline to creatine ratio (greater than 1.3) indicated the presence of tumor, demonstrating that 3-T MR spectroscopy can provide valuable information for diagnosing glioma recurrence after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo 3-T MR spectroscopy in the distinction of recurrent glioma versus radiation effects: initial experience. Rabinov, JD., Lee, PL., Barker, FG., et al.[2022]

Citations

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Hyperpolarized 13C magnetic resonance metabolic imaging The 13C 2D MRSI data demonstrated excellent detection of 13C-labeled lactate and pyruvate resonances in both the normal rats and the rats with tumors. The [1-13 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7442089/

Monitoring Early Changes in Tumor Metabolism in Response ... This study shows the use of hyperpolarized 13C magnetic resonance spectroscopic imaging (MRSI) to assess therapeutic efficacy in a preclinical tumor model.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0093775404003252

Proton magnetic resonance spectroscopic evaluation of ... This review covers the basic physics of 1H-MRS, the spectral and physiological characteristics of the metabolites that are typically measured in various types ...

4. aacrjournals.org aacrjournals.org/cancerres/article/78/14/3755/631786/Metabolic-Imaging-of-the-Human-Brain-with

Metabolic Imaging of the Human Brain with Hyperpolarized 13 ... Hyperpolarized (HP) MRI using [1-13C] pyruvate is a novel method that can characterize energy metabolism in the human brain and brain tumors.

5. nature.com nature.com/articles/s44303-023-00004-0

Imaging cancer metabolism using magnetic resonance In this Perspective I briefly review and discuss the relative advantages and disadvantages of magnetic resonance imaging of tumour metabolism.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8272438/

Clinical applications of magnetic resonance spectroscopy ... MRS requires no injected contrast agent and no ionizing radiation is involved, which are obvious safety benefits. There are many applications of ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04908709

Spectroscopic MRI Guided Proton Therapy in Assessing ... This trial studies how well spectroscopic magnetic resonance imaging (MRI) guided proton therapy works in assessing metabolic change in pediatric patients with ...

8. ajnr.org ajnr.org/content/25/10/1696

Brain Tumor Classification by Proton MR Spectroscopy Our results suggest that short TE 1 H MR spectroscopy (TE = 30 in this study) produces a slightly more accurate diagnostic outcome in general.

9. nature.com nature.com/articles/nm0396-323

Accurate, noninvasive diagnosis of human brain tumors by ... Proton magnetic resonance spectroscopy is a safe, noninvasive means of performing biochemical analyses in vivo.