Enhanced MRI for Bladder Cancer Staging

Overseen By Dawn McBride, RN

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Jodi Maranchie

Disqualifiers: Metastatic disease, Pregnancy, UTI, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

42 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase Ib study of the safety and performance of a novel intravesical contrast-enhanced Magnetic Resonance Imaging protocol for determination of bladder cancer stage prior to transurethral resection of bladder tumor (21 subjects) or prior to radical cystectomy for muscle invasive disease (21 subjects). Subjects will undergo a single MRI study: a pre-contrast, single breath hold image followed by sterile placement of a temporary urethral catheter for instillation of a 50mL solution containing Gadobutrol (4 mM) plus ferumoxytol (5 mM) and then a second, post-contrast image. Images will be reviewed by two dedicated abdominal radiologists, who are blinded to the pathologic staging, for determination of tumor presence and depth of bladder wall penetration.

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 Ferumoxytol, Feraheme, Gadobutrol, Gadavist, Gadobutrol Injection for bladder cancer staging?

Research shows that using gadolinium-based contrast agents in MRI can improve the accuracy of staging bladder cancer, with a study reporting an 83% accuracy rate in identifying tumor stages. Additionally, ferumoxtran-10, a similar agent to ferumoxytol, has been evaluated for its effectiveness in imaging lymph nodes in bladder cancer patients. ^{1 2 3 4 5}

Is gadobutrol safe for use in humans?

Gadobutrol, a contrast agent used in MRI scans, has been shown to be generally safe and well-tolerated in a wide range of patients, including children and adults with various health conditions. It has a low risk of causing nephrogenic systemic fibrosis, a rare condition associated with some contrast agents, and has been used safely in over 50 million doses. ^{6 7 8 9 10}

How does enhanced MRI differ from other treatments for bladder cancer staging?

Enhanced MRI for bladder cancer staging is unique because it uses contrast agents like gadolinium to improve the visibility of tumors and their spread, offering better accuracy in identifying the extent of cancer compared to traditional imaging methods. This approach allows for more precise staging, especially for tumors that are difficult to detect with other techniques. ^{2 3 4 5 11}

Research Team

Jodi K Maranchie, MD

Principal Investigator

Associate Professor

Eligibility Criteria

This trial is for adults aged 18-90 with bladder cancer, either scheduled for tumor removal or with muscle-invasive disease suitable for surgery. Participants must be able to consent, have a performance status of ECOG 0 or 1 (fully active or restricted in physically strenuous activity), and normal kidney function. Pregnant women, those with severe allergies to contrast agents used in MRI, extreme claustrophobia, incompatible implants, metastatic disease, urinary infections or urethral strictures cannot join.

Inclusion Criteria

I am fully active or can carry out light work.

Able to understand and willing to sign a written informed consent document

I have a bladder tumor scheduled for removal or a muscle-invasive bladder cancer suitable for surgery.

Exclusion Criteria

You have had a serious allergic reaction to gadobutrol or ferumoxytol.

I have a urinary tract infection that hasn't been treated.

I am not pregnant, breastfeeding, or planning to become pregnant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Imaging

Participants undergo a single MRI study with pre-contrast and post-contrast imaging to assess bladder cancer stage

1 day

1 visit (in-person)

Surgical Procedure

Participants proceed with their scheduled surgical procedure (TURBT or radical cystectomy) as per standard of care

1 day

Follow-up

Participants are monitored for safety and effectiveness after the imaging and surgical procedures

4 weeks

Long-term Safety Monitoring

Characterize the safety profile of MRI imaging by soliciting and recording adverse events

2 years

Treatment Details

Interventions

• Ferumoxytol
• Gadobutrol

Trial Overview The study tests a new MRI protocol using Gadobutrol and Ferumoxytol as contrast agents to determine the stage of bladder cancer before surgery. Patients will receive one pre-contrast image followed by an instillation of the contrast solution through a catheter and then a post-contrast image. Two radiologists blind to pathology results will assess tumor presence and invasion depth.

Participant Groups

Group I: Magnetic Resonance Imaging Experimental Treatment 3 Interventions

Prior to planned surgical resection, subjects will undergo a single Magnetic Resonance Imaging study: a single breath-hold pre-contrast image followed by sterile placement of a temporary urethral catheter for instillation of a 50mL solution containing Gadobutrol (4 mM) plus ferumoxytol (5 mM) and a second, single breath hold post-contrast image.

Who Is Running the Clinical Trial?

Jodi Maranchie

Lead Sponsor

Trials

2

Recruited

80+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study involving 14 rabbits with VX2 tumors, 1.0-M gadobutrol provided significantly higher tumor enhancement compared to 0.5-M gadopentetate dimeglumine during MRI, indicating its superior efficacy as a contrast agent.

Despite both agents showing similar diagnostic performance in terms of sensitivity and specificity, readers preferred 1.0-M gadobutrol for its better lesion delineation and contrast, suggesting it may improve the quality of tumor imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic contrast-enhanced magnetic resonance imaging evaluation of VX2 carcinoma in a rabbit model: comparison of 1.0-M gadobutrol and 0.5-M gadopentetate dimeglumine. Chang, JM., Moon, WK., Cha, JH., et al.[2016]

Ferumoxtran-10-enhanced magnetic resonance imaging significantly improves the accuracy of nodal staging in bladder cancer patients, with postcontrast imaging showing a sensitivity increase from 76% to 96% for detecting pelvic metastases.

This imaging technique can identify metastases in normal-sized lymph nodes that would otherwise be missed, demonstrating its potential to enhance diagnostic capabilities in bladder cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urinary bladder cancer: preoperative nodal staging with ferumoxtran-10-enhanced MR imaging. Deserno, WM., Harisinghani, MG., Taupitz, M., et al.[2016]

In a study of 60 patients with suspected bladder tumors, gadolinium-enhanced MRI demonstrated an 83% accuracy in staging infiltrating tumors, with a sensitivity of 86% and specificity of 83%.

The use of gadolinium contrast significantly improved the localization of tumors, revealing three tumors that were not detectable without it, although small papillary tumors and carcinoma in situ still posed challenges for accurate preoperative staging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gadolinium-enhanced magnetic resonance imaging in the staging of urinary bladder neoplasms. Sohn, M., Neuerburg, J., Teufl, F., et al.[2018]

Dynamic gadolinium-enhanced MRI (DGE-MRI) demonstrated good sensitivity (87.5%) for detecting organ-confined bladder cancer, but its specificity (47.6%) was lower, indicating it may not reliably distinguish between different stages of the disease.

In detecting lymph node-positive disease, DGE-MRI showed a sensitivity of only 40.7% but a high specificity of 91.5%, suggesting it is better at confirming the absence of disease rather than its presence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative staging of invasive bladder cancer with dynamic gadolinium-enhanced magnetic resonance imaging: results from a prospective study. Daneshmand, S., Ahmadi, H., Huynh, LN., et al.[2015]

MRI demonstrated moderate accuracy in staging bladder cancer, correctly identifying the T stage in 63% of 100 patients with transitional cell carcinoma, with good agreement in differentiating between non-invasive and muscle-invasive disease.

The addition of gadolinium-enhanced sequences provided minimal benefit, improving staging accuracy in only three patients, suggesting that routine use of these enhanced images is unnecessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bladder cancer: evaluation of staging accuracy using dynamic MRI. Rajesh, A., Sokhi, HK., Fung, R., et al.[2022]

Gadobutrol, a second-generation gadolinium-based contrast agent, is effective for enhancing MRI images across various medical fields, allowing for better visualization of pathological lesions and improved diagnostic capabilities.

It is generally well tolerated in a wide range of patients, including those with renal or hepatic impairments, and has a lower risk of causing nephrogenic systemic fibrosis compared to older linear GBCAs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gadobutrol: a review of its use for contrast-enhanced magnetic resonance imaging in adults and children. Scott, LJ.[2021]

In a study involving 229 adult patients with suspected brain tumors, gadobutrol and gadoteridol were found to provide similar effectiveness in enhancing MR imaging for lesion detection and characterization, despite gadobutrol being at a higher concentration.

There were no significant differences in adverse events between the two contrast agents, indicating that both are safe options for patients undergoing brain imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are there differences between macrocyclic gadolinium contrast agents for brain tumor imaging? Results of a multicenter intraindividual crossover comparison of gadobutrol with gadoteridol (the TRUTH study). Maravilla, KR., Smith, MP., Vymazal, J., et al.[2021]

Gadobutrol, a gadolinium-based contrast agent, demonstrated a high safety margin in preclinical studies, with no adverse effects observed at doses 10 to 12 times higher than the standard diagnostic dose used in humans (0.1 mmol/kg).

The compound was well tolerated in animal studies, showing no teratogenic effects and no indications of genotoxicity or immunotoxicity, making it a safe option for use in magnetic resonance imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicological safety evaluation of gadobutrol. Wack, C., Steger-Hartmann, T., Mylecraine, L., et al.[2019]

Gadobutrol, a macrocyclic contrast agent, has an excellent safety profile, with only 4.0% of patients experiencing adverse events in clinical trials, comparable to other contrast agents.

The safety of gadobutrol was confirmed across various patient populations, including children and those with renal or hepatic impairments, with serious adverse reactions being very rare in over 5.7 million administrations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of gadobutrol, a new generation of contrast agents: experience from clinical trials and postmarketing surveillance. Voth, M., Rosenberg, M., Breuer, J.[2014]

Gadobutrol is a safe and effective gadolinium-based contrast agent for MRI, with over 20 years of clinical experience and more than 50 million doses administered, showing a low risk of nephrogenic systemic fibrosis (NSF).

Its unique formulation, with a higher gadolinium ion concentration, allows for improved image enhancement during diagnostic procedures, making it suitable for a wide range of patients, including those with renal or hepatic impairments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gadobutrol: A Review in Contrast-Enhanced MRI and MRA. Scott, LJ.[2022]

Gadolinium-enhanced dynamic MR imaging significantly improves the visualization and staging accuracy of bladder tumors confined to the bladder wall (stages pT1-pT3a), achieving an accuracy of 85% in a study of 79 patients with 86 tumors.

This technique outperformed conventional MR imaging and CT scans, which had accuracies of only 58% and 55%, respectively, highlighting its potential for better diagnosis and treatment planning in bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bladder tumor staging: comparison of conventional and gadolinium-enhanced dynamic MR imaging and CT. Tanimoto, A., Yuasa, Y., Imai, Y., et al.[2016]

References

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

Dynamic contrast-enhanced magnetic resonance imaging evaluation of VX2 carcinoma in a rabbit model: comparison of 1.0-M gadobutrol and 0.5-M gadopentetate dimeglumine. [2016]

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

Urinary bladder cancer: preoperative nodal staging with ferumoxtran-10-enhanced MR imaging. [2016]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Gadolinium-enhanced magnetic resonance imaging in the staging of urinary bladder neoplasms. [2018]

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

Preoperative staging of invasive bladder cancer with dynamic gadolinium-enhanced magnetic resonance imaging: results from a prospective study. [2015]

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

Bladder cancer: evaluation of staging accuracy using dynamic MRI. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Gadobutrol: a review of its use for contrast-enhanced magnetic resonance imaging in adults and children. [2021]

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

Are there differences between macrocyclic gadolinium contrast agents for brain tumor imaging? Results of a multicenter intraindividual crossover comparison of gadobutrol with gadoteridol (the TRUTH study). [2021]

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

Toxicological safety evaluation of gadobutrol. [2019]

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

Safety of gadobutrol, a new generation of contrast agents: experience from clinical trials and postmarketing surveillance. [2014]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Gadobutrol: A Review in Contrast-Enhanced MRI and MRA. [2022]

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

Bladder tumor staging: comparison of conventional and gadolinium-enhanced dynamic MR imaging and CT. [2016]