Use of Quantitative Ultrasound to Guide Adaptive Chemotherapy Among Women With Breast Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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This study phase II will demonstrate the use of quantitative ultrasound to guide adaptive chemotherapy for patients with breast cancer. The primary endpoint will be measurement of improved response rate locally. This trial will enroll 240 randomized breast cancer patients to be assess with quantitative ultrasound to guide adaptive neoadjuvant chemotherapy as compared to standard clinical monitoring and therapy. We will evaluate the safety of its use and expect equivalence in this small patient population. This will allow for more accurate estimation of a needed sample size for a phase III superiority trial.

Official Title
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A Phase II Study of Quantitative Ultrasound to Guide Adaptive Chemotherapy Among Women With Locally Advanced Breast Cancer (LABC)

Conditions
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Breast Cancer

Intervention / Treatment
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* Device: Quantitative ultrasound to guide adaptive chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women ≥ 18 years of age Diagnosis of breast cancer with a primary tumour >2cm in size With conditions meeting criteria for chemotherapy administration Normal hematological blood counts (hemoglobin ≥ 100 g/l, platelet count ≥ 100 x 109, absolute neutrophil count ≥ 2.0 x109 cells per L) Creatinine ≤175 µmol/L Liver enzymes (AST and ALT) ≤ 1.5 times upper limit of normal Cardiac function (left ventricular ejection fraction) ≥55% Eligible for neoadjuvant chemotherapy. Exclusion Criteria: Inflammatory breast cancer Contraindications to neoadjuvant treatment including pregnancy or lactation Past medical history of connective tissue disease Past history of dermatologic disease involving the breast Eastern Cooperative Group Status (ECOG) ≥3 No peripheral neuropathy of a severity of grade ≥2 Evidence of distant metastatic disease Known sensitivity to components present in ultrasound gel.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The trial design is a Phase II study to demonstrate the use of quantitative ultrasound to guide adaptive chemotherapy for patients with breast cancer. The primary endpoint will be measurement of improved response rate locally. Patients were randomly allocated in 1:1 ratio to a standard arm or experimental arm stratified by hormonal receptor status
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard Neoadjuvant Chemotherapy Monitoring<br>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. | |
| Experimental: Adaptive Chemotherapy Monitoring<br>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. | Device: Quantitative ultrasound to guide adaptive chemotherapy<br>* Quantitative ultrasound results will be used to measure chemotherapy response and guide an adaptive chemotherapy strategy for patients who are found to be nonresponders to their chemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measuring the rate of treatment response between the treatment groups | 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. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical efficacy of quantitative ultrasound | Sensitivity and specificity of quantitative ultrasound will be calculated against surgical pathologic response documented after surgery. | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ultrasound, Chemotherapy