DSC-MRI for Recurrent Glioblastoma

Recruiting in Palo Alto (17 mi)

+51 other locations

Overseen by Jerrold Boxerman

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: ECOG-ACRIN Cancer Research Group

Must be taking: Bevacizumab

Must not be taking: Immunotherapies

Disqualifiers: Pregnancy, Intratumoral hemorrhage, others

No Placebo Group

Breakthrough Therapy

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI) works in measuring relative cerebral blood volume (rCBV) for early response to bevacizumab in patients with glioblastoma that has come back. DSC-MRI may help evaluate changes in the blood vessels within the cancer to determine a patient?s response to treatment.

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does require that you have not been previously treated with immunotherapies.

What data supports the effectiveness of the drug Bevacizumab for treating recurrent glioblastoma?

Research shows that using a special type of MRI scan called DSC-MRI to measure blood flow in the brain can help predict how well patients with recurrent glioblastoma respond to Bevacizumab. This drug, which targets blood vessel growth in tumors, has shown promise in improving outcomes for these patients. ^{1 2 3 4 5}

Is bevacizumab safe for humans?

Bevacizumab has been studied for safety in humans, and while it is generally considered safe, it can have serious side effects. Some of these include gastrointestinal perforation (a hole in the stomach or intestines), venous thromboembolism (blood clots in veins), and intracranial hemorrhages (bleeding in the brain), especially in patients with glioblastoma. It's important to monitor for these risks and manage them appropriately. ^{3 6 7 8 9}

How is the drug Bevacizumab unique for treating recurrent glioblastoma?

Bevacizumab is unique because it targets and inhibits VEGF (a protein that promotes blood vessel growth), which is crucial in reducing the blood supply to tumors. This approach is different from traditional treatments, as it focuses on cutting off the tumor's blood supply rather than directly attacking the tumor cells. ^{1 2 3 5 10}

Research Team

Jerrold Boxerman

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for adults with recurrent glioblastoma who can undergo MRI scans and have not been treated with immunotherapies. They must have a Karnofsky performance status of at least 70, no severe allergies to gadolinium, no MR-incompatible implants, and adequate organ function. Pregnant or breastfeeding women are excluded.

Inclusion Criteria

I have never received immunotherapy treatments.

My kidneys work well (eGFR >= 40).

My weight is within the limit for an MRI scanner table.

Exclusion Criteria

Progressive enhancement on MRI within specified timeframes

Intratumoral hemorrhage as seen on hemosiderin-sensitive MRI

I am not taking bevacizumab for reasons unrelated to cancer treatment.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Patients undergo DSC-MRI within 3 days before bevacizumab initiation

1 week

1 visit (in-person)

Treatment

Patients receive bevacizumab and undergo DSC-MRI at day 15 to measure changes in rCBV

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for overall survival and progression-free survival

Up to 5 years

Every 3 months for 1 year, then every 6 months for up to 4 years

Treatment Details

Interventions

• Bevacizumab (Monoclonal Antibodies)
• Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging (Diagnostic Test)

Trial Overview The study tests how well DSC-MRI measures blood volume changes in the brain as an early indicator of response to Bevacizumab treatment in patients experiencing their first recurrence of glioblastoma.

Participant Groups

Group I: Diagnostic (DSC-MRI) Experimental Treatment 1 Intervention

Patients undergo DSC-MRI within 3 days before bevacizumab initiation and at day 15.

Bevacizumab is already approved in Japan, Canada for the following indications:

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

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

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 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 11 patients with recurrent glioblastoma, the use of 18F-fluoroethyl-L-tyrosine (FET) PET imaging showed that a high post-treatment-to-pretreatment FET uptake ratio was linked to poorer progression-free survival (PFS) and overall survival (OS), indicating its potential as a prognostic tool.

The correlation between FET PET uptake and MRI contrast-enhanced T1 signal intensity was moderate, suggesting that while FET PET can provide valuable information, it may not fully differentiate between tumor vascular normalization and actual antitumor effects after bevacizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Voxel-Wise Analysis of Fluoroethyltyrosine PET and MRI in the Assessment of Recurrent Glioblastoma During Antiangiogenic Therapy. George, E., Kijewski, MF., Dubey, S., et al.[2019]

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 258 patients with malignant glioma treated with bevacizumab, the incidence of severe adverse drug reactions was 15.1%, with specific concerns including cerebral bleeding and infections, indicating a manageable safety profile.

The 1-year survival rate for newly diagnosed glioblastoma patients was 78%, suggesting that bevacizumab is effective and comparable to previous clinical trial results, making it a viable treatment option in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of bevacizumab in Japanese patients with malignant glioma: a post-marketing surveillance study. Motoo, N., Hayashi, Y., Shimizu, A., et al.[2020]

Bevacizumab, used to treat glioblastoma and other tumors, has a unique toxicity profile that can lead to serious side effects like gastrointestinal perforation and intracranial hemorrhages, particularly in glioblastoma patients.

The study systematically reviewed these adverse events, identifying risk factors and suggesting preventive and therapeutic measures to reduce treatment-related complications, emphasizing the need for careful monitoring in patients receiving this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical management of bevacizumab-related toxicities in glioblastoma. Brandes, AA., Bartolotti, M., Tosoni, A., et al.[2022]

In a study of 74 patients with recurrent glioblastoma treated with bevacizumab (BEV), 34% developed T1-hyperintense lesions and 47% had diffusion-restricted lesions, indicating significant imaging changes associated with treatment.

Patients with both T1-hyperintense and diffusion-restricted lesions (28% of the cohort) had a notably longer overall survival of 13.0 months compared to 6.6 months for those without these lesions, suggesting that these double-positive lesions may indicate effective antitumor activity and better local control of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained focal antitumor activity of bevacizumab in recurrent glioblastoma. Bähr, O., Harter, PN., Weise, LM., et al.[2022]

Bevacizumab, a monoclonal antibody targeting VEGF, has shown improved patient outcomes in recurrent glioblastoma (GBM) when used in combination with chemotherapy, leading to its accelerated approval by the FDA based on positive results from phase 2 studies.

The treatment is associated with manageable toxicity, as severe adverse events occur in only a small percentage of patients, making it a safer option for those with recurrent GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab for the treatment of recurrent glioblastoma. Chamberlain, MC.[2023]

In a study of 24 patients with recurrent glioblastoma treated with bevacizumab, a reduction in tumor leakage observed through DSC perfusion MRI at 8 weeks significantly predicted longer overall survival (OS) and progression-free survival (PFS).

Higher baseline leakage levels were linked to a greater reduction in leakage after treatment, suggesting that baseline leakage could serve as a potential biomarker for predicting treatment response, although it was not directly associated with survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leakage decrease detected by dynamic susceptibility-weighted contrast-enhanced perfusion MRI predicts survival in recurrent glioblastoma treated with bevacizumab. Hilario, A., Sepulveda, JM., Hernandez-Lain, A., et al.[2022]

References

1. 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]

2. 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]

3. Italy pubmed.ncbi.nlm.nih.gov

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

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

Voxel-Wise Analysis of Fluoroethyltyrosine PET and MRI in the Assessment of Recurrent Glioblastoma During Antiangiogenic Therapy. [2019]

5. England pubmed.ncbi.nlm.nih.gov

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

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

Safety and effectiveness of bevacizumab in Japanese patients with malignant glioma: a post-marketing surveillance study. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Practical management of bevacizumab-related toxicities in glioblastoma. [2022]

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

Sustained focal antitumor activity of bevacizumab in recurrent glioblastoma. [2022]

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

Bevacizumab for the treatment of recurrent glioblastoma. [2023]

10. Italy pubmed.ncbi.nlm.nih.gov

Leakage decrease detected by dynamic susceptibility-weighted contrast-enhanced perfusion MRI predicts survival in recurrent glioblastoma treated with bevacizumab. [2022]