Contrast Agents for Detecting Liver Metastases

Overseen By Samuel Chang, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Colorado, Denver

Disqualifiers: Age, Low eGFR, Gadolinium allergy, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a faster and potentially cheaper MRI method using gadobenate dimeglumine is as effective as the current method with gadoxetate disodium in detecting liver metastases from colorectal cancer. Participants will undergo two MRI scans, each using one of the contrast agents, to compare their effectiveness. The trial seeks individuals with colorectal cancer who have had prior imaging suggesting liver metastases but have not yet received any treatment, including surgery. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, and it seeks to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What is the safety track record for these treatments?

Research has shown that both gadobenate dimeglumine (MultiHance) and gadoxetate disodium (Eovist) are generally safe for liver MRIs. Studies have found that MultiHance is well-tolerated by patients and effective for liver imaging, with no major safety concerns. Similarly, several studies have tested Eovist, confirming its strong safety profile. It is considered safe even for patients with varying kidney function.

Both contrast agents are widely used in medical imaging and provide reliable results without significant side effects. This makes them good options for those considering participation in a clinical trial focused on liver imaging. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using gadobenate dimeglumine and gadoxetate disodium as contrast agents to detect liver metastases. Unlike traditional imaging techniques, these agents offer enhanced sensitivity and specificity in identifying cancerous lesions in the liver, particularly those from colorectal cancer (CRC). This can lead to earlier and more accurate detection of metastases, potentially improving treatment planning and outcomes. Additionally, the unique properties of gadoxetate disodium allow for better visualization of liver tissue, which can be crucial for precise diagnosis and staging of liver lesions. Overall, these advancements in imaging could revolutionize how liver metastases are detected and managed.

What evidence suggests that this trial's treatments could be effective for detecting liver metastases?

This trial will compare the effectiveness of gadobenate dimeglumine and gadoxetate disodium in detecting liver metastases from colorectal cancer. Research has shown that both agents effectively identify liver cancer spread. Studies indicate that MRIs using gadobenate dimeglumine are 95.1% sensitive and have a 90.9% positive predictive value (PPV) for detecting liver cancer spots, demonstrating high accuracy in identifying cancer in the liver. In contrast, gadoxetate disodium detected more cancer spots than traditional scans in 40% of patients. Both agents perform well, but they might offer slightly different advantages in spotting liver cancer spread. Participants in this trial will undergo exams with both agents in a randomized order to assess their comparative effectiveness. ^{3 4 6 7 8}

Who Is on the Research Team?

Nikhil Madhuripan, MD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with colorectal cancer who have suspected liver metastases and haven't had any treatments, including surgery. It's not suitable for those with poor kidney function, non-MR safe implants, a history of bad reactions to gadolinium contrast agents, claustrophobia or movement disorders.

Inclusion Criteria

I have colorectal cancer.

Prior imaging with suspected liver metastasis

I have not had any treatment, including surgery, for my condition.

Exclusion Criteria

Previous reaction to gadolinium contrast agents

History of claustrophobia or movement disorders likely to impact image quality

My kidney function is severely reduced.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging Protocol Comparison

Participants undergo two complete protocol liver MRs for known or suspected CRC metastasis, one exam with gadoxetate disodium and the other exam with gadobenate dimeglumine, within an interval of 3-10 days, in opposite order.

3-10 days

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging procedures

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Gadobenate dimeglumine
• Gadoxetate disodium

Trial Overview

The study compares two MRI contrast agents: Gadoxetate disodium (standard care) versus Gadobenate dimeglumine (potential time and cost saver). The goal is to see if the latter can detect liver metastases from colorectal cancer as effectively as the former.

How Is the Trial Designed?

Group I: Gadoxetate disodium exam first Active Control 2 Interventions

The subjects will be randomized into two groups. Both groups will undergo two complete protocol liver MRs for known or suspected CRC metastasis, one exam with gadoxetate disodium and the other exam with gadobenate dimeglumine, within an interval of 3-10 days, but in opposite order, determined randomly.

Group II: Gadobenate Dimeglumine exam first Active Control 2 Interventions

The subjects will be randomized into two groups. Both groups will undergo two complete protocol liver MRs for known or suspected CRC metastasis, one exam with gadoxetate disodium and the other exam with gadobenate dimeglumine, within an interval of 3-10 days, but in opposite order, determined randomly.

Gadobenate dimeglumine is already approved in United States, European Union for the following indications:

Approved in United States as MultiHance for:

• Central nervous system imaging
• Liver imaging
• Vascular imaging

Approved in European Union as MultiHance for:

• Hepatic imaging
• Pelvic imaging
• Cardiac imaging
• Brain and spine imaging
• Musculoskeletal imaging

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Bracco Diagnostics, Inc

Industry Sponsor

Trials

62

Recruited

9,500+

Diana Bracco

Bracco Diagnostics, Inc

Chief Executive Officer since 1999

Degree in Chemistry from the University of Pavia

Alberto Spinazzi

Bracco Diagnostics, Inc

Chief Medical Officer since 2023

MD

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 140 pediatric MRI cases using gadoxetate disodium, transient severe respiratory motion occurred in 7.84% of non-sedated patients, which is lower than the 5-22% reported in adult studies.

No cases of transient severe respiratory motion were observed in sedated patients, suggesting that sedation may effectively eliminate this issue during imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rate of gadoxetate disodium (Eovist®) induced transient respiratory motion in children and young adults. Lanier, H., Wallace, A., Khanna, G.[2021]

In a study of 127 patients with liver nodules, gadobenate dimeglumine and gadoxetate disodium showed similar rates of arterial phase hyperenhancement, indicating both contrast agents are effective for this feature in liver imaging.

However, gadobenate dimeglumine was superior in visualizing dynamic phase washout and the capsule feature, suggesting it may provide better overall imaging for hepatocellular carcinoma detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Visualization Rates of LI-RADS Version 2014 Major Features With IV Gadobenate Dimeglumine or Gadoxetate Disodium in Patients at Risk for Hepatocellular Carcinoma. Allen, BC., Ho, LM., Jaffe, TA., et al.[2019]

In a study of 10,595 patients undergoing MRI with gadolinium-based contrast agents, the overall incidence of acute adverse reactions was low at 0.45%, with no severe reactions reported.

Younger patients were found to be at a higher risk for experiencing acute adverse reactions, and gadoxetate disodium had a higher incidence of reactions (0.82%) compared to gadopentetate dimeglumine (0.43%), indicating that while all agents are generally safe, some may carry slightly more risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and severity of acute adverse reactions to four different gadolinium-based MR contrast agents. Okigawa, T., Utsunomiya, D., Tajiri, S., et al.[2019]

Magnetic resonance imaging (MRI) is highly effective for diagnosing liver and bile duct issues in children, with noncontrast MRI showing good results due to the visibility of bile.

Using the hepatocyte-specific contrast agent gadoxetate disodium (Eovist) enhances MRI by providing better characterization of liver lesions through its partial excretion, although there are specific applications and limitations to consider in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Eovist in Pediatric Patients: Pearls and Pitfalls. Shet, NS., Flynn, JF., Maloney, E., et al.[2021]

The study demonstrated that using a combination of gadoxetic acid (GA) and gadobenate dimeglumine (GD) in liver MRI can create a 'plain-white-liver' effect, enhancing the visibility of liver structures and potentially improving the detection of metastases.

Optimal imaging conditions were identified, with the best contrast achieved 60-120 seconds after GD administration and using a lower dose of GA (0.025 mmol/kg), suggesting that this protocol could enhance sensitivity in detecting liver lesions in future patient studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined gadoxetic acid and gadobenate dimeglumine enhanced liver MRI: a parameter optimization study. Knobloch, G., Colgan, T., Wang, X., et al.[2021]

Gadobenate dimeglumine (MultiHance) demonstrated significantly higher sensitivity for detecting intracranial metastases (93%-100%) compared to other MRI contrast agents, which had sensitivity rates of only 65%-73%.

The increased lesion-to-brain contrast with gadobenate dimeglumine (+43%) compared to comparator agents (+27%) suggests that its higher relaxivity contributes to its superior efficacy in identifying metastatic lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of intracranial metastases: a multicenter, intrapatient comparison of gadobenate dimeglumine-enhanced MRI with routinely used contrast agents at equal dosage. Colosimo, C., Ruscalleda, J., Korves, M., et al.[2019]

In a study involving 12 patients at risk for hepatocellular carcinoma (HCC), gadoxetic acid showed higher sensitivity for HCC detection compared to gadopentetate dimeglumine for one of the observers, indicating it may be more effective in identifying liver tumors.

Both contrast agents provided similar image quality, but gadoxetic acid enhanced lesion conspicuity and liver-to-lesion contrast during the hepatobiliary phase, suggesting it may offer better visualization of HCC in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of gadoxetic acid and gadopentetate dimeglumine-enhanced MRI for HCC detection: prospective crossover study at 3 T. Besa, C., Kakite, S., Cooper, N., et al.[2020]

In a review of safety data from 12 clinical studies involving 1989 patients, gadoxetate disodium showed a high safety profile, with only 10.1% of patients reporting adverse events, and only 4.1% classified as related to the drug.

The most common related adverse events were nausea and headache, each occurring in 1.1% of patients, and the safety profile remained consistent across various patient subgroups, including those with liver cirrhosis or impaired function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of gadoxetate disodium: Results from the clinical phase II-III development program and postmarketing surveillance. Endrikat, JS., Dohanish, S., Balzer, T., et al.[2022]

Gadoxetate acid (Gd-EOB-DTPA) is a safe and effective liver-specific contrast agent that enhances MRI imaging, improving the detection and characterization of hepatocellular carcinoma (HCC) compared to unenhanced MRI and other imaging methods.

The use of gadoxetate acid allows for better differentiation of early HCC from benign or premalignant nodules, which is crucial for determining appropriate management strategies and improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gadoxetate Acid-Enhanced MR Imaging for HCC: A Review for Clinicians. Chanyaputhipong, J., Low, SC., Chow, PK.[2021]

A total of 424 risk signals related to adverse events (AEs) were identified from the FAERS database for four gadolinium-based contrast agents (GBCAs) over an 18-year period, highlighting significant safety concerns associated with these agents.

The study revealed that some adverse events linked to GBCAs were not included in their package inserts, indicating a need for further research to ensure patient safety and awareness of potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Data mining and analysis of the adverse events derived signals of 4 gadolinium-based contrast agents based on the US Food and drug administration adverse event reporting system. Wang, L., Wang, Y., Zhao, Q.[2023]

In a study involving 8194 patients across multiple countries, gadoxetate disodium was found to have a low adverse event rate of 1.7%, indicating it is generally safe for routine use in liver MRI.

The most common adverse events were mild, such as dyspnea and nausea, and importantly, no serious adverse events were related to the drug in the pediatric population, highlighting its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of gadoxetate disodium: results from six clinical phase IV studies in 8194 patients. Endrikat, J., Kim, SY., Sakaguchi, T., et al.[2018]

Gadoxetic acid-enhanced MRI is significantly more sensitive than contrast-enhanced CT for detecting liver metastases, especially for lesions smaller than 1 cm, making it a valuable diagnostic tool.

This imaging technique provides both dynamic and static liver-specific information, which can improve treatment planning for patients with liver metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current evidence for the diagnostic value of gadoxetic acid-enhanced magnetic resonance imaging for liver metastasis. Tsurusaki, M., Sofue, K., Murakami, T.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3269572/

MRI of colorectal cancer liver metastases: comparison of orally ...

The metastasis-to-liver SI ratio was significantly higher after CMC-001 than after gadobenate dimeglumine (0.51 and 0.21 respectively, P < 0.0001). More AE ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/30915560/

Detection of liver metastases on gadobenate dimeglumine ...

The meta-analysis showed an overall sensitivity of 95.1% and PPV of 90.9% of gadobenate-enhanced MRI for the detection of metastases, when based ...

3.

withpower.com

withpower.com/trial/phase-4-neoplasm-metastasis-5-2021-d295e

Contrast Agents for Detecting Liver Metastases

The study demonstrated that using a combination of gadoxetic acid (GA) and gadobenate dimeglumine (GD) in liver MRI can create a 'plain-white-liver' effect, ...

4.

dirjournal.org

dirjournal.org/pdf/beb8919b-f013-4ea1-b1c8-40332e840fe1/articles/56550/Diagn%20Interv%20Radiol-12-22-En.pdf

Contrast agents used in MR imaging of the liver

Detection of liver metastases: gadobenate dimeglumine-enhanced three- dimensional dynamic phases and one- hour delayed phase MR imaging versus.

5.

bracco.com

bracco.com/sites/default/files/2022-10/kr-en-2016-04-30-brochure-the-strenght-of-relaxivity-multihance.pdf

MultiHance®

MultiHance is a paramagnetic contrast agent for use in diagnostic magnetic resonance imaging (MRI) indicated for: • MRI of the liver for the detection of focal ...

6.

bracco.com

bracco.com/sites/default/files/2022-10/kr-en-2016-04-30-brochure-multihance-in-mra-multihance.pdf

MultiHance in MRA

MultiHance is a paramagnetic contrast agent for use in diagnostic magnetic resonance imaging (MRI) indicated for: MRI of the liver for the detection of focal ...

7.

medsafe.govt.nz

medsafe.govt.nz/profs/datasheet/m/MultiHanceinj.pdf

MultiHance® (dimeglumine gadobenate)

Delayed, liver-specific imaging can be performed between 40 and 120 minutes following the injection, depending on the individual imaging needs.

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S0273230017304038

Non-clinical assessment of safety and gadolinium ...

Non-clinical assessment of safety and gadolinium deposition after cumulative administration of gadobenate dimeglumine (MultiHance®) to neonatal and juvenile ...