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?

The purpose of this study is to compare a special type of mammogram that uses a contrast agent called contrast-enhanced digital mammography with contrast-enhanced digital breast tomosynthesis (CEDM+CEDBT), with breast magnetic resonance imaging imaging (MRI) for predicting the effect of neoadjuvant chemotherapy on pathologic complete response rates. The device used to obtain CEDM+CEDBT images is called Siemens MAMMOMAT. This device produces two-dimensional (2D) images, as in a normal mammogram, but also collects additional images for digital breast tomosynthesis (DBT), which produces a three-dimensional (3D) image of the breast in the form of image slices. DBT allows the radiologist to "see through" the breast tissue for better detection and localization of breast cancer. By looking at both the CEDM images and the CEDBT images, a radiologist may be able to better detect residual breast cancer in a more cost-effective manner. Participation may last up to 18 weeks. Study procedures for this research are: * Undergoing 1-2 mammograms during and/or after your chemotherapy, but before primary breast surgery. * Before each mammogram, have a radiology technician inject a liquid contrast agent by inserting a needle into a vein. The chemotherapy port cannot be used to receive the contrast agent * Let the research team record information from your medical record related to your condition and the treatment you receive. * Give permission to collect leftover tissue from your diagnostic biopsy and breast surgery.

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.

Is Omnipaque (Iohexol) generally safe for use in humans?

Omnipaque (Iohexol) is generally well-tolerated in humans, with fewer side effects compared to some other contrast media. However, it can cause minor skin reactions and, in rare cases, changes in neurological status or minor heart rate changes. In animal studies, it was found to be more irritating to the lungs than previously thought. ^{1 2 3 4 5}

How does contrast-enhanced mammography differ from other breast cancer treatments?

Contrast-enhanced mammography (CEM) is unique because it uses an iodine-containing contrast medium to improve the visibility of breast tumors, which is not a feature of standard mammography. This method allows for better detection and characterization of lesions by producing enhanced images through a combination of low and high energy exposures. ^{6 7 8 9 10}

What data supports the effectiveness of the drug Omnipaque 350mgI/mL Solution for Injection, Iohexol, Omnipaque 350?

Research shows that Iohexol, the active ingredient in Omnipaque, is effective in providing clear images for various types of medical imaging, such as urography, angiography, and myelography, with good tolerance and minimal adverse reactions in patients. ^{4 5 11 12 13}

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

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

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 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 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 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]

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 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]

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 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]

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]

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 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]

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]

Citations

1. Ireland 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. [2013]

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

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

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

Myelography using iohexol (Omnipaque). [2015]

4. England pubmed.ncbi.nlm.nih.gov

Comparison of low-osmolar contrast media in paediatric cardiac angiography. [2015]

5. Sweden pubmed.ncbi.nlm.nih.gov

Iohexol in coronary angiography. A double blind investigation. [2019]

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

Direct effects of contrast media on rat lungs. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

Iohexol compared to meglumine-Ca-metrizoate in common carotid angiography. A randomized double blind cross-over study in man. [2019]

8. Japan pubmed.ncbi.nlm.nih.gov

[Clinical analysis of drug eruption due to iohexol (Omnipaque)]. [2013]

9. Germany pubmed.ncbi.nlm.nih.gov

Technique, protocols and adverse reactions for contrast-enhanced spectral mammography (CESM): a systematic review. [2020]

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

Contrast-enhanced digital mammography: initial clinical experience. [2022]

11. Ireland pubmed.ncbi.nlm.nih.gov

Low energy mammogram obtained in contrast-enhanced digital mammography (CEDM) is comparable to routine full-field digital mammography (FFDM). [2022]

12. Germany pubmed.ncbi.nlm.nih.gov

[Use of contrast-enhanced mammography for diagnosis of breast cancer]. [2023]

13. Korea (South) pubmed.ncbi.nlm.nih.gov

Contrast-enhanced spectral mammography: comparison with conventional mammography and histopathology in 152 women. [2018]