Contrast-Enhanced Mammography for Breast Cancer

Overseen By Caterina Vacchi-Suzzi, PhD

Age: 18+

Sex: Female

Trial Phase: Phase < 1

Sponsor: Alison Stopeck

Disqualifiers: Pregnancy, Allergy to contrast, Diabetes, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a special type of mammogram can better predict breast cancer treatment effectiveness compared to an MRI. It employs a contrast-enhanced digital mammogram and tomosynthesis (a 3D imaging technique) to obtain clearer breast images. The contrast agent used is Omnipaque 350mgI/mL Solution for Injection (also known as Iohexol or Omnipaque 350). Women diagnosed with locally advanced breast cancer, who are scheduled to receive at least four cycles of chemotherapy before surgery, might be suitable candidates. Participants will undergo mammograms during or after chemotherapy and allow the collection of some medical information and leftover tissue samples. As an Early Phase 1 trial, this research focuses on understanding the imaging technique's function in people, offering participants a chance to contribute to groundbreaking advancements in breast cancer diagnostics.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the trial involves imaging and contrast agents, it's best to discuss your medications with the research team to ensure there are no interactions.

What prior data suggests that the Siemens MAMMOMAT device is safe for use in breast cancer imaging?

Research has shown that Omnipaque, the contrast dye used in this trial, is usually well-tolerated and has been widely used in imaging tests. Studies have found it safe for most people. However, some individuals might experience reactions, which can occur immediately after the injection or a few hours later. Common reactions include a warm sensation or a metallic taste in the mouth. Serious reactions, such as allergic responses or kidney problems, are rare but can occur, particularly in those with existing health issues. Participants should discuss any concerns with their healthcare provider before joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about contrast-enhanced mammography (CEDM) for breast cancer because it offers a new way to visualize tumors, potentially leading to more accurate assessments. Unlike traditional mammograms, which rely solely on X-rays, CEDM uses a contrast dye (Omnipaque 350mgI/mL) to highlight blood vessels in and around cancerous tissues. This technique helps doctors see tumor details more clearly, especially after chemotherapy, potentially leading to better treatment planning before surgery. By providing enhanced imaging, CEDM could improve the precision of breast cancer evaluations compared to standard mammography.

What evidence suggests that this imaging technique is effective for detecting breast cancer?

Previous studies have shown that contrast-enhanced mammography (CEM) effectively detects breast cancer. One study demonstrated that individuals with breast cancer are over eight times more likely to have a positive CEM result than those without cancer, highlighting its diagnostic power. In this trial, participants will undergo a combination of CEM and contrast-enhanced digital breast tomosynthesis (CEDBT) imaging. Digital breast tomosynthesis (DBT) creates 3D images that help doctors see through breast tissue more clearly. Together, CEM and DBT serve as powerful tools for detecting and assessing breast cancer, especially in dense breast tissue. ^{5 6 7 8 9}

Who Is on the Research Team?

Alison Stopeck, MD

Principal Investigator

Stony Brook Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with early-stage, invasive breast cancer who are planning to undergo at least four cycles of neoadjuvant chemotherapy before surgery. Participants will have mammograms using a contrast agent during/after chemo but before surgery.

Inclusion Criteria

I have been diagnosed with advanced breast cancer, regardless of hormone or HER2 status.

I am scheduled for at least 4 rounds of chemotherapy before surgery.

Exclusion Criteria

Pregnancy

Allergy/sensitivity to contrast agent

I have diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive neoadjuvant chemotherapy, with imaging occurring after every 4-6 cycles

12-16 weeks

1-2 imaging visits

Imaging and Surgery Preparation

Participants undergo CEDM + CEDBT imaging and prepare for definitive breast surgery

2 weeks

1-2 imaging visits

Follow-up

Participants are monitored for safety and effectiveness after surgery

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Omnipaque 350mgI/mL Solution for Injection

Trial Overview The study compares contrast-enhanced digital mammography (CEDM) and digital breast tomosynthesis (CEDBT) against MRI in predicting the effectiveness of pre-surgery chemotherapy on eliminating cancer cells.

How Is the Trial Designed?

Group I: CEDM + CEDBT Experimental Treatment 3 Interventions

Participants undergo CEDM + CEDBT imaging after every 4-6 cycles of neoadjuvant chemotherapy prior to surgery (imaging may occur up to 2 times)

Who Is Running the Clinical Trial?

Alison Stopeck

Lead Sponsor

Trials

4

Recruited

220+

Published Research Related to This Trial

In a report of 7 cases, Iohexol (Omnipaque), a nonionic X-ray contrast agent, caused drug eruptions characterized by generalized edematous and erythematous plaques, but without severe adverse reactions.

The eruptions typically appeared 5 to 6 days post-examination in non-sensitized patients, or within hours in sensitized patients, indicating a potential for cross-sensitization among nonionic contrast agents, though no cross-sensitization with ionic contrast media was observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical analysis of drug eruption due to iohexol (Omnipaque)]. Akiyama, M., Iijima, M., Fujisawa, R.[2013]

In a randomized double-blind cross-over study comparing iohexol and meglumine-Ca-metrizoate, iohexol was found to have significantly fewer side effects, indicating it may be a safer option for patients.

While both contrast media caused some heart rate changes, the occurrence of a short asystolic period after injecting meglumine-Ca-metrizoate in two patients suggests it may have a higher toxicity risk compared to iohexol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iohexol compared to meglumine-Ca-metrizoate in common carotid angiography. A randomized double blind cross-over study in man. Nakstad, P., Sortland, O., Aaserud, O.[2019]

In a study involving 62 children with congenital heart disease, no significant differences were found in hemodynamic changes or angiographic quality between the contrast agents iohexol and iopamidol after cardiac angiography.

Both contrast agents were assessed for their effects on systolic pressure, end-diastolic pressure, heart rate, and plasma osmolality, indicating that they are similarly safe and effective for use in pediatric cardiac imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of low-osmolar contrast media in paediatric cardiac angiography. Rubin, CM., Ogilvie, BC., Keeton, BR.[2015]

Contrast-enhanced mammography (CEM) offers improved visualization of breast tumors, particularly beneficial for women with dense breast tissue, compared to traditional mammography.

CEM is recommended when magnetic resonance imaging (MRI) is not an option, and while its use in breast cancer screening is currently debated, it may gain importance as more data from large studies become available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of contrast-enhanced mammography for diagnosis of breast cancer]. Fischer, U., Diekmann, F., Helbich, T., et al.[2023]

In a study involving 17 patients with a history of adverse reactions to contrast media, iohexol was used for brain CT enhancement without premedication, resulting in only one mild skin reaction after 24 hours.

Five patients received multiple iohexol injections on different occasions without experiencing any adverse reactions, suggesting that iohexol may be a safe option for patients with previous contrast media sensitivities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iohexol in patients with previous adverse reactions to contrast media. Holtås, S.[2019]

In a study involving 30 patients undergoing myelography with iohexol, adverse reactions were observed in 4 patients, indicating a low but notable risk associated with the procedure.

The neurological status of 2 patients showed slight changes, and minor EEG changes were noted in 1 patient, suggesting that while the procedure is generally safe, monitoring for neurological effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myelography using iohexol (Omnipaque). Peeters, F.[2015]

In a phase II study involving 117 patients across three different applications (urography, cardioangiography, and cerebral angiography), iohexol (Omnipaque) demonstrated good efficacy in providing X-ray opacity and was well tolerated without any unexpected severe reactions.

The positive results from these initial studies support the advancement of iohexol into phase III trials for further evaluation as a contrast medium.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II studies in urography, cardioangiography and cerebral angiography with iohexol. An evaluation of the clinical trial program and the clinical findings. Andrew, E., Sveen, K., Renaa, T., et al.[2013]

In a study involving 30 patients, Iohexol (Omnipaque) demonstrated excellent image quality in coronary angiography, comparable to the routine contrast medium meglumine, Na-Ca-metrizoate (Isopaque Coronar).

The study reported minimal adverse reactions, with only one case of hypotension, indicating that Iohexol is a safe and effective option for selective coronary angiography.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iohexol in coronary angiography. A double blind investigation. Orjavik, OS., Orning, OM., Skrede, M., et al.[2019]

In a study involving 88 women and 170 breasts, low-energy contrast enhanced digital mammography (CEDM) images were found to be equivalent to standard full-field digital mammograms (FFDM) in terms of technical parameters and visibility of mammographic findings.

Using low-energy CEDM can potentially reduce patient radiation exposure while maintaining diagnostic accuracy, making it a viable alternative to standard FFDM for breast cancer evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low energy mammogram obtained in contrast-enhanced digital mammography (CEDM) is comparable to routine full-field digital mammography (FFDM). Francescone, MA., Jochelson, MS., Dershaw, DD., et al.[2022]

Contrast-enhanced spectral mammography (CESM) demonstrated a higher sensitivity for detecting breast cancer (100%) compared to conventional mammography (91%), making it a potentially more effective screening tool.

CESM also showed greater diagnostic accuracy (80%) than conventional mammography (65%), suggesting it may be a better option for preoperative assessment of breast lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast-enhanced spectral mammography: comparison with conventional mammography and histopathology in 152 women. Luczyńska, E., Heinze-Paluchowska, S., Dyczek, S., et al.[2018]

In a study involving 24 rats, full-strength Gastrografin caused immediate death due to severe pulmonary edema, highlighting its dangerous effects if aspirated during medical procedures.

Omnipaque (iohexol) and 3% Gastrografin were not fatal but caused significant lung irritation, with Omnipaque leading to more edema and alveolar hemorrhage compared to normal saline, indicating it is more harmful to lung tissue than previously thought.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct effects of contrast media on rat lungs. Wells, HD., Hyrnchak, MA., Burbridge, BE.[2019]

A systematic review of 84 studies involving 14,012 patients found that contrast-enhanced spectral mammography (CESM) is generally safe, with a low adverse reaction rate of 0.82%, including only one severe non-fatal reaction.

The study highlighted the need for standardization in CESM protocols, as most studies used similar parameters, such as a contrast dose of 1.5 mL/kg at a flow rate of 3 mL/s and a 120-second acquisition delay, but only half of the studies were prospective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technique, protocols and adverse reactions for contrast-enhanced spectral mammography (CESM): a systematic review. Zanardo, M., Cozzi, A., Trimboli, RM., et al.[2020]

In a study involving 22 women suspected of having breast abnormalities, contrast-enhanced digital mammography successfully detected enhancement in 8 out of 10 biopsy-proven cancers, indicating its potential efficacy in identifying malignant lesions.

The study found that while the morphology of lesions generally matched their pathological diagnoses, no enhancement was observed in 7 out of 12 benign cases, suggesting that contrast-enhanced digital mammography could help differentiate between malignant and benign lesions, especially in dense breast tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast-enhanced digital mammography: initial clinical experience. Jong, RA., Yaffe, MJ., Skarpathiotakis, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10680079/

Contrast-Enhanced Mammography in Breast Cancer Screening Contrast-enhanced mammography (CEM) is a promising vascular-based breast imaging technique with high diagnostic performance in detecting breast cancer.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9219005/

Contrast-Enhanced Digital Mammography Screening for ... The positive likelihood ratio of 8.33 suggested that CEDM findings are 8.3 times more likely to be positive in an individual with breast cancer when compared ...

3. cureus.com cureus.com/articles/315605-efficacy-of-contrast-enhanced-mammography-in-the-evaluation-of-breast-lesions-an-initial-experience.pdf?email=

Efficacy of Contrast-Enhanced Mammography in the ... The sensitivity of mammography was found to be significantly reduced to 30% in dense breast parenchyma [4]. Digital breast tomosynthesis (DBT) ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05625659

Comparison of Breast Cancer Screening With CESM to ... Aim 2: To evaluate the performance of CESM compared to DBT at the 1-year follow up for breast-cancer screening in women with dense breasts. Detailed Description.

5. ajronline.org ajronline.org/doi/10.2214/AJR.17.19265

Contrast-Enhanced Mammography: A Systematic Guide to ... This article is to discuss the essential steps involved in performing, interpreting, managing, and reporting findings on contrast-enhanced mammography.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/018956s099lbl.pdf

OMNIPAQUE™ (iohexol) Injection 140 180 240 300 350 140 ... OMNIPAQUE is provided as a sterile, pyrogen-free, colorless to pale-yellow solution, in the following iodine concentrations: 140, 180, 240, 300, and 350 ...

7. gehealthcare.com gehealthcare.com/-/jssmedia/GEHC/US/Files/Products/Contrast-Media/Omnipaque/omnipaque-uspi.pdf?srsltid=AfmBOorK1hbCQN-3xVwacFtQZjDJu0RLRkLjwzghYjhz3oIXyPbtnnGD

omnipaque-uspi.pdf HIGHLIGHTS OF PRESCRIBING INFORMATION. These highlights do not include all the information needed to use. OMNIPAQUE safely and effectively. See full prescribing.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/018956s116%2C020608s049lbl.pdf

OMNIPAQUE (iohexol) oral solution - accessdata.fda.gov Most severe reactions develop shortly after the start of the injection. (within 3 minutes), but reactions can occur up to hours later. There is an increased ...

9. gehealthcare.com gehealthcare.com/products/contrast-media/omnipaque?srsltid=AfmBOopf50dg8eInoFlXS8hwhgKLr1o2zhrWsg7s8Jn5IaGQjFuEN3fi

Omnipaque™ (iohexol) injection Omnipaque has been unsurpassed by any low-osmolar contrast media for tolerability at equi-attenuating doses in head-to-head trials.