Advanced Imaging Techniques for Glioblastoma

(GABLE Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Daniel P Barboriak

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: ECOG-ACRIN Cancer Research Group

Disqualifiers: Pregnancy, Breast-feeding, MRI contraindications, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This phase II trial studies whether different imaging techniques can provide additional and more accurate information than the usual approach for assessing the activity of tumors in patients with newly diagnosed glioblastoma. The usual approach for this currently is magnetic resonance imaging (MRI). This study is trying to learn more about the meaning of changes in MRI scans after treatment, as while the appearance of some of these changes may reflect progressing tumor, some may be due the treatment. Dynamic susceptibility contrast (DSC)-MRIs, along with positron emission tomography (PET) and/or magnetic resonance (MR) spectroscopy, may help doctors tell which changes are a reflection of the treatment and which changes may be due to progressing tumor.

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 data supports the effectiveness of the treatment Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging and bevacizumab for glioblastoma?

Research shows that using dynamic susceptibility contrast MRI to measure blood volume changes can help predict how well patients with recurrent glioblastoma respond to bevacizumab, a drug that targets blood vessel growth in tumors. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

The studies focus on the effectiveness of bevacizumab and advanced imaging techniques in treating glioblastoma, but they do not provide specific safety data for these treatments. Bevacizumab has been used in various conditions, suggesting it is generally considered safe, but specific safety details are not provided in these studies. ^{1 3 5 6 7}

How does this treatment differ from other treatments for glioblastoma?

This treatment uses advanced imaging techniques, like dynamic susceptibility contrast MRI, to monitor blood flow and volume in the brain, which helps predict how well a patient is responding to treatments like bevacizumab. This approach is unique because it provides detailed insights into the tumor's blood supply, potentially allowing for more personalized and effective treatment plans. ^{1 2 3 5 8}

Research Team

Daniel P Barboriak

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

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

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

I am 18 years old or older.

A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets specific criteria

Trial Timeline

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

Treatment Details

Interventions

• Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging (Procedure)
• Fluciclovine F18 (Radiopharmaceutical)
• Gadolinium-Chelate (Contrast Agent)
• Magnetic Resonance Spectroscopy (Procedure)
• Positron Emission Tomography (Procedure)

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.

Participant Groups

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+

Dr. Peter J. O'Dwyer

ECOG-ACRIN Cancer Research Group

Chief Executive Officer since 2012

MD from University of Pennsylvania

Dr. Mitchell D. Schnall

ECOG-ACRIN Cancer Research Group

Chief Medical Officer since 2012

MD, PhD from University of Pennsylvania

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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 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]

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]

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 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]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Prognostic value of relative cerebral blood volume in patients with recurrent glioblastoma multiforme treated with bevacizumab. [2020]

2. England 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. [2022]

3. England 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. [2019]

4. England 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. [2022]

5. England 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. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Relative cerebral blood volume is a potential predictive imaging biomarker of bevacizumab efficacy in recurrent glioblastoma. [2018]

7. Switzerland 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Impact of imaging measurements on response assessment in glioblastoma clinical trials. [2021]