Ultrasound-Guided Chemotherapy for Breast Cancer

Overseen By Gregory J Czarnota, PhD, MD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Sunnybrook Health Sciences Centre

Disqualifiers: Inflammatory breast cancer, Pregnancy, Connective tissue disease, 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)

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

240 Participants Needed

Trial Summary

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 Ultrasound-Guided Chemotherapy for Breast Cancer?

Research shows that quantitative ultrasound (QUS) can effectively predict how breast cancer patients will respond to chemotherapy, with an accuracy of up to 88%. QUS can also monitor changes in tumors early in treatment, helping to predict patient outcomes and survival rates. ^{1 2 3 4 5}

How does ultrasound-guided chemotherapy differ from other breast cancer treatments?

Ultrasound-guided chemotherapy for breast cancer is unique because it uses quantitative ultrasound (QUS) to non-invasively monitor and predict how well a patient will respond to chemotherapy. This method can provide early insights into treatment effectiveness by analyzing changes in tissue structure, which helps tailor treatments to individual patients more effectively than traditional methods. ^{1 2 3 4 6}

What is the purpose of this trial?

The primary objective of this study is to assess the feasibility of randomizing breast cancer patients to quantitative ultrasound to guide adaptive Neoadjuvant Chemotherapy as compared to standard clinical monitoring and therapy. The Investigators have previously demonstrated that high-frequency ultrasound and spectroscopy, and recently conventional-frequency ultrasound and spectroscopy may be used to detect cell death in vitro, in situ and in vivo. The method can detect different forms of cell death and has been demonstrated to be sensitive to apoptotic, necrotic and mitotic cell death. By detecting cell death early in a treatment on the order of hours to days, rather than traditional anatomical assessments that take place weeks to months after the completion of therapy, ineffective therapies could be switched to more efficacious treatments or aggressive salvage therapy which has shown to already benefit patients. The overarching goal of this research is to transform the delivery of neoadjuvant chemotherapy using quantitative ultrasound (QUS), which is non-invasive, inexpensive and portable.

Research Team

Gregory J Czarnota, PhD, MD

Principal Investigator

Sunnybrook Health Sciences Centre

Eligibility Criteria

This trial is for women over 18 with breast cancer tumors larger than 2cm who are eligible for chemotherapy. They must have normal liver enzymes, cardiac function, creatinine levels, and blood counts. It's not for those with skin diseases affecting the breast, inflammatory breast cancer, contraindications like pregnancy or past connective tissue disease.

Inclusion Criteria

My breast cancer tumor is larger than 2cm.

I am a woman aged 18 or older.

Your liver enzymes (AST and ALT) should be within a certain range, not too high.

Exclusion Criteria

I do not have severe nerve damage.

My cancer has spread to distant parts of my body.

I need help with my daily activities due to my health condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adaptive neoadjuvant chemotherapy guided by quantitative ultrasound or standard neoadjuvant chemotherapy

12 weeks

Visits at Pre-treatment, Weeks 1, 4, 8, 12, and Pre-Operatively

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• Quantitative Ultrasound

Trial Overview The study tests if using quantitative ultrasound (QUS) to monitor cell death can guide adjustments in neoadjuvant chemotherapy more effectively than standard monitoring. The goal is to identify ineffective treatments early and switch to better options quickly.

Participant Groups

Group I: Adaptive Chemotherapy Monitoring Experimental Treatment 1 Intervention

Patients who will be randomized to the experimental arm Adaptive Chemotherapy Monitoring and demonstrate Response (+) will continue until standard chemotherapy is completed. For patients who do not demonstrate response after 4 weeks of chemotherapy, an early switch to the second phase of chemotherapy could occur (Phase II/Taxane) At the discretion of the treating medical oncologist. Patients will undergo Quantitative Ultrasound on the following time points: Pre-treatment, Weeks 1, 4, 8, 12 and Pre-Operatively. These QUS time points correspond to the following chemotherapy times.

Group II: Standard Neoadjuvant Chemotherapy Monitoring Active Control 1 Intervention

Patients who will be randomized to the control arm with Standard Neoadjuvant Chemotherapy Monitoring will receive Phase I chemotherapy consisting of anthracycline-based treatment followed by Phase II chemotherapy consisting of taxane-based treatment. Patients will be imaged but no modifications to treatment will occur in this trial arm depending on response by quantitative ultrasound.

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Findings from Research

Quantitative ultrasound (QUS) can effectively predict the response of breast cancer patients to neoadjuvant chemotherapy (NAC) with an impressive accuracy of 88%, based on a study of 56 patients.

QUS features were found to be more effective than molecular markers in predicting patient outcomes, including five-year recurrence-free survival, highlighting its potential as a non-invasive diagnostic tool.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A priori Prediction of Neoadjuvant Chemotherapy Response and Survival in Breast Cancer Patients using Quantitative Ultrasound. Tadayyon, H., Sannachi, L., Gangeh, MJ., et al.[2018]

Quantitative ultrasound (QUS) imaging can effectively and non-invasively monitor the response of breast cancer patients to chemotherapy, with a study involving 100 patients showing high accuracy in predicting treatment responses.

QUS biomarkers that assess intra-tumour heterogeneity can predict patient outcomes with accuracies ranging from 82% to 89% at different time points after treatment initiation, indicating that this method could help tailor cancer treatments to individual patients based on their early response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy-Response Monitoring of Breast Cancer Patients Using Quantitative Ultrasound-Based Intra-Tumour Heterogeneities. Sadeghi-Naini, A., Sannachi, L., Tadayyon, H., et al.[2020]

Quantitative ultrasound (QUS) can effectively predict recurrence in patients with locally advanced breast cancer during neoadjuvant chemotherapy, with a study of 83 patients showing that the k-NN classifier achieved an accuracy of 81% at week 4.

Incorporating texture derivatives from QUS data significantly improved prediction accuracy, increasing the area under the curve (AUC) from 0.70 to 0.83, indicating that treatment-related changes provide valuable insights for predicting clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Changes in Quantitative Ultrasound Imaging Parameters during Neoadjuvant Chemotherapy to Predict Recurrence in Patients with Locally Advanced Breast Cancer. Bhardwaj, D., Dasgupta, A., DiCenzo, D., et al.[2022]

Quantitative ultrasound (QUS) parameters can predict tumor response to neoadjuvant chemotherapy (NAC) in locally advanced breast cancer patients, with accuracy improving from 60% at week 1 to 80% at week 4.

Combining pre-treatment QUS data with measurements taken during treatment enhances prediction accuracy and may help tailor personalized treatment plans for patients with refractory tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative ultrasound assessment of breast tumor response to chemotherapy using a multi-parameter approach. Tadayyon, H., Sannachi, L., Gangeh, M., et al.[2023]

Quantitative ultrasound (QUS) is a promising non-invasive technique that effectively monitors treatment responses by correlating ultrasound backscatter parameters with cell death, making it useful for evaluating tumor responses.

Clinical studies have successfully used QUS to differentiate between benign and malignant breast lesions, as well as to identify patients who respond to treatment, highlighting its potential in improving cancer diagnosis and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementation of Non-Invasive Quantitative Ultrasound in Clinical Cancer Imaging. Sharma, D., Osapoetra, LO., Czarnota, GJ.[2022]

Quantitative ultrasound (QUS) effectively monitored tumor cell death in breast cancer cells treated with hyperthermia (HT) and ultrasound-stimulated microbubbles (USMB), showing significant increases in ultrasound parameters after treatment, particularly at 50 minutes of HT exposure.

The study found a strong correlation between QUS texture features and histopathological findings, indicating that QUS can be a reliable noninvasive imaging technique to assess the effectiveness of anticancer treatments in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive Evaluation of Breast Tumor Response to Combined Ultrasound-Stimulated Microbubbles and Hyperthermia Therapy Using Quantitative Ultrasound-Based Texture Analysis Method. Sharma, D., Sannachi, L., Osapoetra, LO., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

A priori Prediction of Neoadjuvant Chemotherapy Response and Survival in Breast Cancer Patients using Quantitative Ultrasound. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Chemotherapy-Response Monitoring of Breast Cancer Patients Using Quantitative Ultrasound-Based Intra-Tumour Heterogeneities. [2020]

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

Early Changes in Quantitative Ultrasound Imaging Parameters during Neoadjuvant Chemotherapy to Predict Recurrence in Patients with Locally Advanced Breast Cancer. [2022]

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

Quantitative ultrasound assessment of breast tumor response to chemotherapy using a multi-parameter approach. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Implementation of Non-Invasive Quantitative Ultrasound in Clinical Cancer Imaging. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Noninvasive Evaluation of Breast Tumor Response to Combined Ultrasound-Stimulated Microbubbles and Hyperthermia Therapy Using Quantitative Ultrasound-Based Texture Analysis Method. [2023]