Contrast-Enhanced Ultrasound for Cervical Cancer

Overseen By Ji-Bin Liu, MD

Age: 18+

Sex: Female

Trial Phase: Phase < 1

Sponsor: Thomas Jefferson University

Disqualifiers: Pregnancy, Nursing, Unstable cardiac arrhythmias, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to identify sentinel lymph nodes, crucial for understanding cancer spread, in women with cervical, vaginal, or vulvar cancer. It employs ultrasound with a special contrast agent, Sonazoid (also known as Perflubutane), which contains tiny bubbles to enhance node visibility. The trial aims to determine if this method outperforms current practices. Women with these cancers who can adhere to the study's protocol may be suitable candidates. This research could advance the diagnosis and treatment of these cancers. As an Early Phase 1 trial, it focuses on understanding how this new method works in people, offering participants the opportunity to contribute to groundbreaking advancements in cancer diagnosis.

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

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have received an investigational drug in the 30 days before the study or will receive one within 72 hours afterwards, you cannot participate.

What prior data suggests that this ultrasound technique with Sonazoid is safe for detecting sentinel lymph nodes?

Research has shown that Sonazoid, a substance used to enhance ultrasound images, is generally safe for patients. Studies have found it to be well-tolerated, with no major side effects reported. For instance, when used for liver imaging, Sonazoid did not cause any serious side effects and was considered safe for patients with liver issues. Another study confirmed its safety when administered intravenously, showing that patients handled it well. These findings suggest that Sonazoid is a safe option for improving ultrasound images in various medical situations. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for cervical cancer involve surgery, radiation, or chemotherapy, which can be quite invasive and have significant side effects. However, researchers are excited about using contrast-enhanced ultrasound with Sonazoid because it provides a non-invasive way to enhance imaging. The unique feature of this approach is the use of perflubutane microbubbles, which are injected and then visualized using ultrasound. This method could potentially improve the precision of cancer detection and treatment planning, helping doctors target the cancer more effectively. By enhancing imaging, it may lead to better outcomes with fewer side effects compared to traditional treatments.

What evidence suggests that this ultrasound method is effective for detecting sentinel lymph nodes in cervical cancer?

Research has shown that Sonazoid, a special dye used in ultrasound scans, can identify sentinel lymph nodes (SLNs) more effectively than usual methods. In this trial, participants will receive perflubutane microbubble injections, known as Sonazoid, followed by an ultrasound. Studies indicate that ultrasounds with Sonazoid distinguish between cancerous and non-cancerous tissues better than regular ultrasounds. Specifically, it has proven more effective in diagnosing breast lumps and differentiating between cancerous and non-cancerous growths in the uterine lining. The tiny bubbles in Sonazoid enhance ultrasound images, aiding doctors in spotting SLNs more easily. These findings suggest that using Sonazoid could lead to more accurate cancer diagnoses and improved treatment planning. ^{2 6 7 8 9}

Who Is on the Research Team?

Ji-Bin Liu, MD

Principal Investigator

Thomas Jefferson University

Are You a Good Fit for This Trial?

This trial is for women over 18 with cervical, vaginal, or vulvar cancer who can follow study procedures. They must not be pregnant/nursing and have no recent surgeries, unstable heart conditions, severe allergies to Sonazoid/eggs, or been on life support recently.

Inclusion Criteria

I have been diagnosed with cancer of the cervix, vagina, or vulva.

I am female.

If of child-bearing potential, must have a negative pregnancy test

Exclusion Criteria

Patients who have received an investigational drug in the 30 days before study drug administration, or will receive one within 72 hours afterwards

I was born with a heart defect.

I do not have serious heart rhythm problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Diagnostic Procedure

Patients receive perflubutane microbubble injections subdermally and then undergo ultrasound over 30 minutes before standard of care cancer treatment

30 minutes

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Sonazoid

Trial Overview The trial tests a new ultrasound technique using Sonazoid contrast to find sentinel lymph nodes against the standard detection methods in female reproductive cancers. The goal is to see if this method identifies more lymph nodes.

How Is the Trial Designed?

Group I: Diagnostic (perflubutane microbubble, ultrasound) Experimental Treatment 2 Interventions

Patients receive perflubutane microbubble injections subdermally and then undergo ultrasound over 30 minutes before standard of care cancer treatment.

Who Is Running the Clinical Trial?

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Contrast-enhanced ultrasound (CEUS) using Sonazoid significantly improved the accuracy of diagnosing focal breast lesions compared to unenhanced ultrasound, with an accuracy rate of 87.2% versus 65.5%.

CEUS also demonstrated higher specificity than both unenhanced ultrasound and contrast-enhanced MRI, while maintaining a low incidence of mild adverse reactions (3.3%), indicating it is a safe and effective diagnostic tool.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of sonazoid (perflubutane) for contrast-enhanced ultrasound in the differentiation of focal breast lesions: phase 3 multicenter clinical trial. Miyamoto, Y., Ito, T., Takada, E., et al.[2016]

In a study of 31 patients with focal nodular hyperplasia (FNH) of the liver, contrast-enhanced ultrasonography (CEUS) using Sonazoid revealed characteristic vascular patterns, including central artery and stellate vascularity in 77.4% of lesions.

Most lesions (93.5%) remained either hyperechoic or isoechoic during the Kupffer phase, indicating that CEUS can effectively aid in the noninvasive diagnosis of FNH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focal Nodular Hyperplasia of the Liver: Contrast-Enhanced Ultrasonographic Features With Sonazoid. Lee, J., Jeong, WK., Lim, HK., et al.[2022]

Using Sonazoid for contrast-enhanced ultrasonography (CEUS) significantly improves the detection of hepatocellular carcinoma (HCC) in patients with liver cirrhosis, leading to an increase in life expectancy by 1.99 quality-adjusted life-years (QALY).

CEUS surveillance is cost-effective, with an incremental cost-effectiveness ratio (ICER) of $18,384 per QALY, which is below the commonly accepted threshold of $50,000/QALY, making it a viable option for HCC surveillance globally.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis on the surveillance for hepatocellular carcinoma in liver cirrhosis patients using contrast-enhanced ultrasonography. Tanaka, H., Iijima, H., Nouso, K., et al.[2020]

Quantitative contrast-enhanced ultrasonography (CEUS) effectively detects changes in cervical tumor perfusion after one cycle of neoadjuvant chemotherapy (NACT) in 38 patients with stage IB2 or IIA cervical cancer, indicating its potential as a predictive tool for treatment response.

Significant correlations were found between pre-treatment maximum intensity (IMAX) values and changes in tumor perfusion, suggesting that lower pre-treatment IMAX may predict a better response to NACT, even before observable size changes occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can quantitative contrast-enhanced ultrasonography predict cervical tumor response to neoadjuvant chemotherapy? Peng, C., Liu, LZ., Zheng, W., et al.[2018]

In a study of 51 patients with locally advanced cervical cancer, 2D and 3D transvaginal ultrasound (TV-US) demonstrated high diagnostic accuracy for evaluating parametrial involvement after neoadjuvant chemotherapy, achieving a sensitivity of 100% post-treatment.

The agreement between ultrasound and MRI in identifying parametrial infiltration was strong, with a concordance rate of 90% after chemotherapy, suggesting that TV-US could be a reliable method for assessing treatment response and could be integrated into preoperative evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Parametrial Status in Locally Advanced Cervical Cancer Patients after Neoadjuvant Chemotherapy: A Prospective Study on Diagnostic Accuracy of Three-Dimensional Transvaginal Ultrasound. Perniola, G., Fischetti, M., Tomao, F., et al.[2020]

In a study of 49 women with cervical cancer and 21 healthy controls, contrast-enhanced ultrasonography (CEUS) showed a significant difference in contrast distribution, with 89% of women with tumors exhibiting focal contrast compared to only 3% of healthy participants.

Semi-quantitative analysis of CEUS parameters demonstrated high accuracy in distinguishing tumors from healthy tissue, with area under the curve (AUC) values of 0.92 and 0.94 for total contrast and maximal intensity, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Study on Diagnostic Performance of Contrast-Enhanced Ultrasonography for Detection of Early Cervical Cancer. Pálsdóttir, K., Epstein, E.[2019]

Transrectal ultrasonography (TRUS) is effective for accurately measuring tumor size in advanced-stage cervical cancer before treatment, showing consistent results with clinical examinations and MRI.

Post-therapy evaluations are more accurately performed with MRI, as the use of contrast agents in both TRUS and MRI did not enhance the accuracy of tumor assessments either before or after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimodal endocavitary ultrasound versus MRI and clinical findings in pre- and post-treatment advanced cervical cancer. Preliminary report. Csutak, C., Badea, R., Bolboaca, SD., et al.[2018]

In a study of 108 patients with cervical cancer, contrast-enhanced ultrasound (CEUS) showed strong correlation with MRI in measuring tumor size and assessing local invasion, indicating it is a reliable alternative for evaluation.

CEUS is a less expensive and non-invasive method for assessing tumor size and invasion in cervical cancer, demonstrating good concordance with MRI for detecting invasions to surrounding structures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast-enhanced ultrasonography vs MRI for evaluation of local invasion by cervical cancer. Zheng, W., Chen, K., Peng, C., et al.[2020]

In a study of 88 women with locally advanced cervical cancer, 2D grayscale ultrasound showed a sensitivity of 64.6% and specificity of 65% in detecting residual disease after neoadjuvant treatment, indicating moderate diagnostic performance.

Color Doppler ultrasound improved sensitivity to 87.1% for detecting residual disease but had low specificity (21.4%), while the best results for identifying macroscopic residual disease (≥ 6 mm) were achieved with a 2D ultrasound cut-off of 12 mm, yielding a sensitivity of 95% and specificity of 70.6%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PRospective Imaging of CErvical cancer and neoadjuvant treatment (PRICE) study: role of ultrasound to assess residual tumor in locally advanced cervical cancer patients undergoing chemoradiation and radical surgery. Testa, AC., Moro, F., Pasciuto, T., et al.[2018]

In an animal study with 6 beagle dogs, the ultrasound contrast agent Sonazoid demonstrated a dose-dependent increase in acoustic intensity in brain tissue, indicating its effectiveness for visualizing brain perfusion.

Sonazoid provided a more uniform contrast enhancement in gray-scale harmonic imaging compared to harmonic power Doppler imaging, although it also caused some signal attenuation in deeper brain regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Harmonic imaging of the brain parenchyma in a dog model following NC100100 (Sonazoid) bolus injection. Meyer, K., Seidel, G., Algermissen, C.[2019]

Contrast enhanced ultrasonography (CEUS) using Sonazoid demonstrated diagnostic efficacy for detecting hepatic metastasis that is comparable to 18-fluoro-2-deoxyglucose (FDG) PET/CT, with both methods showing 100% sensitivity.

In a study involving 109 patients with gastrointestinal tract cancer, CEUS and PET/CT had similar specificity and accuracy rates, indicating that CEUS is a viable alternative for diagnosing liver metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic value of sonazoid for hepatic metastasis: comparison with FDG PET/CT. Hiraoka, A., Kume, M., Miyagawa, M., et al.[2016]

In a study of 39 patients with stage IB and II cervical cancer, contrast-enhanced ultrasonography (CEUS) significantly improved the accuracy of tumor size evaluation compared to conventional transabdominal ultrasonography (TA-US), with reliability scores indicating a strong correlation with post-operative pathology.

The combination of transrectal ultrasonography (TR-US) and CEUS provided the highest consistency in tumor staging, comparable to magnetic resonance imaging (MRI), making it a valuable tool for assessing cervical cancer staging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast-Enhanced Ultrasonography for Transabdominal and Transrectal Ultrasound in Staging Cervical Cancer: A Reliability Study. Zhang, J., Xiang, JD., Jia, C., et al.[2023]

Citations

1. ajronline.org ajronline.org/doi/10.2214/AJR.12.10518

Efficacy of Sonazoid (Perflubutane) for Contrast-Enhanced ... The objective of our study was to compare the efficacy of contrast-enhanced ultrasound (CEUS) using the ultrasound contrast agent Sonazoid (perflubutane) with ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24660739/

Efficacy of Sonazoid (Perflubutane) for Contrast-Enhanced ... CEUS using Sonazoid was confirmed to be superior to unenhanced ultrasound for the differential diagnosis (benign vs malignant) of focal breast lesions.

3. nature.com nature.com/articles/s41598-025-13771-0

Perfluorobutane CEUS for early-stage cervical lymphoma Perflubutane CEUS can effectively distinguish between cervical lymphoma and benign LNs. The postvascular phase starfield sign demonstrates ...

4. journals.lww.com journals.lww.com/cancerjournal/fulltext/2024/20070/the_ability_of_contrast_enhanced_ultrasound_with.15.aspx

The ability of contrast-enhanced ultrasound with Sonazoid... Sonazoid-CEUS has higher accuracy, specificity, and comparable sensitivity for differentiating EC from benign endometrial lesions compared with conventional US.

5. pubs.rsna.org pubs.rsna.org/doi/pdf/10.1148/radiol.221465

Contrast-enhanced US with Perfluorobutane to Diagnose ... The use of contrast-enhanced US (CEUS), especially the postvascular phase of CEUS with perfluorobutane contrast material, might contribute to improved diagnosis ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0301562923003150

Safety of Sonazoid in Assisting High-Intensity Focused ... Use of Sonazoid is safe and feasible for improving HIFU ablation efficiency during the treatment of advanced malignant liver lesions.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05105087

NCT05105087 | Gynecological Sentinel Lymph Nodes CEUS Diagnostic procedures, such as ultrasound with Sonazoid, may help identify more SLNs than standard of care in patients with cervical, vaginal, or vulvar cancer.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6607878/

Safety of Perfluorobutane (Sonazoid) in Characterizing ... Sonazoid causes no significant AEs after intravenous injection, and shows good safety and tolerence in patients with focal liver lesion(s)

9. pubs.rsna.org pubs.rsna.org/doi/full/10.1148/radiol.221465

Contrast-enhanced US with Perfluorobutane to Diagnose ... The postvascular phase of CEUS with perfluorobutane demonstrated excellent performance for diagnosing suspicious small lateral cervical LNs in participants ...