Advanced Imaging Techniques for Glioblastoma

(GABLE Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: ECOG-ACRIN Cancer Research Group

Disqualifiers: Pregnancy, Breast-feeding, MRI contraindications, 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

Compensation: Varies

Number of Visits: 2

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests advanced imaging techniques to determine if they provide better insights into tumor activity in individuals newly diagnosed with glioblastoma, a type of brain cancer. The usual imaging method, MRI, sometimes struggles to distinguish whether changes in the tumor result from treatment or cancer progression. By using different scans like Dynamic Susceptibility Contrast (DSC)-MRI, Positron Emission Tomography (PET), and Magnetic Resonance Spectroscopy (MR spectroscopy), researchers aim to make this distinction more clearly. Individuals diagnosed with glioblastoma who are about to start standard treatment might be suitable candidates for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer imaging.

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 is best to discuss this with the trial coordinators or your doctor.

What prior data suggests that these imaging techniques are safe for assessing glioblastoma?

Research has shown that the treatments used in this trial are safe for humans.

Dynamic Susceptibility Contrast-Enhanced MRI uses a special dye to obtain clearer images of blood flow in the brain and is generally well-tolerated. Studies have examined its ability to track tumor growth without identifying major safety issues.

Fluciclovine F18, a tracer used in PET scans to study brain tumors, has been the focus of research that suggests it is safe, with no significant safety problems reported.

Magnetic Resonance Spectroscopy (MRS) uses magnetic fields to examine brain metabolism. It does not require injections or radiation, making it safer than some other imaging methods. Studies support its safety.

These treatments have undergone further safety testing, especially since this trial is in a later phase. This suggests they are generally well-tolerated, but like any medical procedure, there can be risks. Participants should discuss any concerns with their doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these advanced imaging techniques for glioblastoma because they offer a more detailed view of the tumor's behavior and response to treatment. Unlike traditional MRI, Dynamic Susceptibility Contrast-Enhanced MRI and Magnetic Resonance Spectroscopy provide rich information on blood flow and chemical changes in the tumor. Meanwhile, Fluciclovine F18 PET scans help visualize metabolic activity, which can reveal tumor growth earlier than standard imaging. These techniques could lead to more personalized treatment plans by identifying aggressive tumors sooner and tracking how well the treatments are working.

What evidence suggests that these imaging techniques are effective for assessing glioblastoma?

In this trial, participants will undergo advanced imaging techniques to assess glioblastoma activity. Research has shown that a special type of MRI, called DSC-MRI, can help predict the recurrence of glioblastoma, a type of brain tumor. This imaging method uses a contrast dye to create detailed pictures of blood flow in the brain, revealing tumor activity. Participants will receive DSC-MRI scans at specific intervals. Additionally, some participants will undergo 18F-Fluciclovine PET scans, which studies have found can accurately differentiate between actual tumor growth and treatment-induced changes, known as pseudoprogression. Magnetic Resonance Spectroscopy (MRS) is another technique used in this trial, effective in distinguishing between real tumor growth and treatment-related changes. Overall, these advanced imaging techniques offer promising insights into glioblastoma activity, potentially leading to better treatment decisions. ^{2 6 7 8 9}

Who Is on the Research Team?

Daniel P Barboriak

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly diagnosed glioblastoma (GBM), confirmed by pathology and who have had surgery within the last 7 weeks. Participants must be in good enough health to perform daily activities (Karnofsky Performance Status ≥ 60%) and plan to receive standard GBM treatment. They should have completed certain MRIs, not be allergic to imaging agents, and able to tolerate MRI procedures.

Inclusion Criteria

My MGMT methylation status is being tested.

I had surgery to diagnose my brain tumor less than 7 weeks ago.

Patient must have no contraindications to MRI, including injection of gadolinium-based contrast agents, and demonstrated ability to tolerate MRI on pre-surgical imaging

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Participants complete standard of care radiation therapy

6 weeks

Imaging Assessment

Participants receive gadolinium-based contrast agent and undergo DSC-MRI scans at 4 and 8 weeks post-radiation therapy. Additional MR spectroscopy or fluciclovine F18 PET scans are conducted if disease progression is evident.

12 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up every 8 weeks for 1 year, then every 12 weeks for 5 years.

6 years

What Are the Treatments Tested in This Trial?

Interventions

• Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging
• Fluciclovine F18
• Gadolinium-Chelate
• Magnetic Resonance Spectroscopy
• Positron Emission Tomography

Trial Overview The study tests if advanced brain scan techniques like Fluciclovine F18 PET scans, Dynamic Susceptibility Contrast-Enhanced MRI, Gadolinium-Chelate enhanced images, and Magnetic Resonance Spectroscopy can more accurately assess tumor activity in patients with new glioblastoma compared to usual MRI methods.

How Is the Trial Designed?

Group I: Diagnostic (DSC-MRI, fluciclovine F18 PET, MR spectroscopy) Experimental Treatment 5 Interventions

Patients receive a gadolinium-based contrast agent and undergo DSC-MRI scans at 4 and 8 weeks after completion of SOC radiation therapy. Patients with evidence of disease progression then undergo MR spectroscopy or receive fluciclovine F18 IV and undergo PET scan within 12 weeks of SOC radiation therapy completion.

Who Is Running the Clinical Trial?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 20 patients with newly diagnosed glioblastoma, the combination of bevacizumab with conventional therapy was well tolerated, showing no severe treatment-related adverse events and resulting in a median progression-free survival (PFS) of 9.66 months and overall survival (OS) of 15.89 months.

Imaging biomarkers from 18F-RGD PET/CT indicated that a significant decrease in SUVmean was associated with better PFS, while a small decrease in Ktrans from DCE-MRI suggested improved OS, highlighting the potential of these imaging techniques to predict treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential 18F-RGD PET/CT and DCE-MRI Imaging-Based Biomarkers for Postoperative Survival Prediction Among Patients With Newly Diagnosed Glioblastoma Treated With Bevacizumab and Chemoradiotherapy. Li, L., Liu, N., Zhang, H., et al.[2022]

Current imaging techniques like T1 +/- contrast and T2/FLAIR are essential for assessing tumor activity in recurrent glioblastoma, but their effectiveness is limited by inconsistent measurement and image acquisition standards across different institutions.

There is a pressing need for standardized MRI protocols and further validation of advanced imaging methods, such as diffusion MRI and amino acid PET, to improve the accuracy of response assessments in clinical trials for glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of imaging measurements on response assessment in glioblastoma clinical trials. Reardon, DA., Ballman, KV., Buckner, JC., et al.[2021]

In a study of 127 patients with recurrent glioblastoma, baseline relative cerebral blood volume (rCBV) was found to be a strong predictor of progression-free survival (PFS) and overall survival (OS) in patients treated with bevacizumab, with 82% of patients achieving 6-month PFS and 79% achieving 12-month OS based on rCBV levels.

The study demonstrated that rCBV is a more effective predictive biomarker for treatment response to bevacizumab compared to conventional MRI volumetric analysis, as it was not associated with survival outcomes in patients receiving alkylating chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative cerebral blood volume is a potential predictive imaging biomarker of bevacizumab efficacy in recurrent glioblastoma. Kickingereder, P., Wiestler, B., Burth, S., et al.[2018]

In a study of 16 high-grade glioma patients treated with bevacizumab (BEV), the volume of gadolinium-based contrast agent (GBCA)-enhancing lesions decreased by 39%, indicating a positive response to treatment.

However, while the overall mean relative blood volume (rCBV) did not significantly decrease, specific areas (hot spots) showed a significant reduction, complicating the differentiation between true tumor progression and pseudoprogression, which could affect clinical management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Misleading early blood volume changes obtained using ferumoxytol-based magnetic resonance imaging perfusion in high grade glial neoplasms treated with bevacizumab. Netto, JP., Schwartz, D., Varallyay, C., et al.[2018]

The study involved 79 MRI examinations in 8 patients with glioblastoma multiforme (GBM) and found that elevated relative cerebral blood volume (rCBV) on perfusion MRI supports the diagnosis of recurrent malignant tumors, indicating its efficacy in monitoring treatment response.

A notable finding was that in some cases, regions with high rCBV were smaller than those with contrast enhancement, suggesting aggressive tumor growth rather than benign changes, highlighting the importance of combining perfusion MRI with conventional MRI for accurate assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic susceptibility contrast-enhanced perfusion magnetic resonance (MR) imaging combined with contrast-enhanced MR imaging in the follow-up of immunogene-treated glioblastoma multiforme. Stenberg, L., Englund, E., Wirestam, R., et al.[2022]

The study created a large-scale radiographic atlas of cerebral blood volume (CBV) using data from 450 patients, which helps in assessing treatment responses in glioblastoma patients more accurately than traditional methods.

In 32 recurrent glioblastoma patients treated with bevacizumab, specific CBV metrics from the atlas, such as a hypervascular tumor volume greater than 2.35 cc before treatment, were linked to shorter progression-free survival (PFS) and overall survival (OS), indicating that this atlas can provide valuable prognostic information.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypervascular tumor volume estimated by comparison to a large-scale cerebral blood volume radiographic atlas predicts survival in recurrent glioblastoma treated with bevacizumab. Leu, K., Enzmann, DR., Woodworth, DC., et al.[2019]

In a study of 13 patients with recurrent glioblastoma multiforme, relative cerebral blood volume (rCBV) measured by dynamic susceptibility contrast MRI was found to be a significant predictor of progression-free survival (PFS) both before and after starting bevacizumab treatment.

Patients with lower rCBV values (less than 4.50 mL/100g at baseline and less than 1.83 mL/100g after treatment) experienced longer PFS, indicating that rCBV can be a reliable biomarker for assessing the effectiveness of antiangiogenic therapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic value of relative cerebral blood volume in patients with recurrent glioblastoma multiforme treated with bevacizumab. Stecco, A., Amatuzzo, P., Sponghini, AP., et al.[2020]

In a study of 36 patients with recurrent high-grade gliomas, pre- and posttreatment relative cerebral blood volume (rCBV) measurements from dynamic MRI were found to be significant predictors of overall survival (OS) and progression-free survival (PFS) when treated with bevacizumab.

Patients with a posttreatment rCBV below 4400 had a significantly longer OS (340 days) compared to those above this threshold (186 days), indicating that lower rCBV values correlate with better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic-susceptibility contrast agent MRI measures of relative cerebral blood volume predict response to bevacizumab in recurrent high-grade glioma. Schmainda, KM., Prah, M., Connelly, J., et al.[2022]

Citations

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Benefits of dynamic susceptibility-weighted contrast ... The specific aim of this article is to review the benefits of DSC perfusion MRI in the therapy of glioma. KEYWORDS : cerebral blood volume, ...

2. ajnr.org ajnr.org/content/early/2022/09/29/ajnr.A7655

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Implementation and evaluation of a dynamic contrast ... In this study we demonstrate the implementation of a post-contrast 3DT1-weighted (3D-T1w) and dynamic contrast-enhancement (DCE) protocol to assess glioblastoma ...

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Reliability of dynamic susceptibility contrast perfusion metrics ... This results in specific perfusion profiles of different subtypes of glioma, as described in a recent review and meta-analysis of our group [2].

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8. sciencedirect.com sciencedirect.com/science/article/abs/pii/B9780128170571000160

Dynamic Susceptibility Contrast MRI: Basic Physics, Pulse ... This chapter details various aspects of DSC-MRI, including basic principles of dose-response and transverse relaxivity of contrast agents, DSC-MRI pulse ...

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Deep learning based on dynamic susceptibility contrast ... In this study, we established and validated two deep learning models for the prediction of early local progression in adult-type diffuse glioma ...