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

Trial Summary

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. ^{1 2 3 4 5}

Is 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. ^{1 6 7 8 9}

How 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. ^{3 10 11 12 13}

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.

Research Team

Jing Wu, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility 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.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

MR-spectroscopy guided target delineation for high-grade gliomas. [2019]

2. Japan pubmed.ncbi.nlm.nih.gov

[Usefulness of Cho/Cr ratio in proton MR spectroscopy for differentiating residual/recurrent glioma from non-neoplastic lesions]. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Intracranial tumors in children: small single-voxel proton MR spectroscopy using short- and long-echo sequences. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Proton MR spectroscopy of intracranial tumours: in vivo and in vitro studies. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

1H-MRS in vivo predicts the early treatment outcome of postoperative radiotherapy for malignant gliomas. [2019]

6. Greece pubmed.ncbi.nlm.nih.gov

Changes in serial magnetic resonance spectroscopy predict outcome in high-grade glioma during and after postoperative radiotherapy. [2011]

7. Switzerland 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. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of radiosurgery to magnetic resonance spectroscopy-defined high-risk tumor volumes in patients with glioblastoma multiforme. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

In vivo 3-T MR spectroscopy in the distinction of recurrent glioma versus radiation effects: initial experience. [2022]

10. Poland pubmed.ncbi.nlm.nih.gov

Magnetic resonance spectroscopy in intracranial tumours of glial origin. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Non-invasive in vivo localized 1H spectroscopy of human astrocytoma implanted in rat brain: regional differences followed in time. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

In vivo 1H NMR spectroscopy of an intracerebral glioma in the rat. [2019]

13. United States pubmed.ncbi.nlm.nih.gov

Spatially localized in vivo 1H magnetic resonance spectroscopy of an intracerebral rat glioma. [2019]