KVUS at Neoadjuvant CTx of Breast Cancer

Study Overview
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Brief Summary
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Effect of the contrast-enhanced diagnostic ultrasound during neoadjuvant chemotherapy of breast cancer on the achieved tumor size reduction and tolerability of chemotherapy

Detailed Description
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The 5-year survival rate of breast cancer patients is decreasing in the advanced, metastatic stage from 99% to 26%. Therefore an optimization of the therapy of advanced breast cancer is urgently needed. To increase the echogenicity of the blood in the ultrasound, microbubbles were developed working as stable, biocompatible contrast agent in ultrasound. Such a clinically approved ultrasound contrast agent is SonoVue® (Bracco International B.V., Amsterdam). SonoVue® is approved by the European Medicines Agency (EMA) (approval number EU/1/01/177/002) for the visualization of focal vascularization lesions of the liver and breast within Doppler sonography and is applied in breast cancer patients primarily for the purpose of diagnosis as well as to evaluate the response to the neoadjuvant used chemotherapy. Animal studies using the contrast enhanced ultrasound have shown that the administration of this contrast agent increases the penetration and accumulation of drugs in the tumor as well as the permeability of the blood-brain barrier resulting in a precise and effective drug distribution. In the tumor animal model it could be shown that a combined treatment with chemotherapy and contrast enhanced ultrasound results in a decreased tumor growth and a prolonged survival. Patients with inoperable pancreatic cancer showed a reduced tumor growth and better tolerability of chemotherapy when administrating the contrast enhanced diagnostic ultrasound during palliative chemotherapy. This could be due to the better tumor response, but also due to the more targeted chemotherapy distribution. The purpose of this study is to examine whether the use of the contrast enhanced diagnostic ultrasound during neoadjuvant chemotherapy results in an increased tumor regression in comparison to native ultrasound. It is an Investigator Initiated Trial and is funded by internal means.

Official Title
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Contrast-enhanced Ultrasound in Neoadjuvant Chemotherapy of Breast Cancer

Conditions
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Early Primary Breast Cancer

Intervention / Treatment
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* Drug: SonoVue


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: written informed consent age > 18 yrs histologically confirmed primary breast cancer including all intrinsic subtypes treatment with neoadjuvant chemotherapy persons who are legally competent and mentally able to follow the instructions of the study team Exclusion Criteria: hypersensitivity / allergy to sulfur hexafluoride, Macrogol 4000, distearoylphosphatidylcholine, dipalmitoylphosphatidylglycerol-sodium, palmitic acid right-left shunt, severe pulmonary hypertension (pulmonary arterial pressure > 90 mmHg) uncontrolled systemic hypertension acute respiratory distress syndrome pregnancy commitment of the patient to any resident institution by order of any court or authority expectation of missing compliance alcohol or drug abuse patients who are in a relationship of dependence or in a working relationship to the sponsor, the investigator or his representative

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Parellel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Application and measurement of tumor size using contrast agent-enhanced diagnostic and therapy supporting (with SonoVue®) ultrasound | Drug: SonoVue<br>* As part of the study therapy supportive ultrasound will be performed with iv Infusion of the chemotherapeutic agent.<br>|
| No Intervention: B<br>Application and measurement of tumor size using contrast agent-enhanced diagnostic ultrasound | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor size reduction (1) | pCR (pathohistological complete remission) | 18 / 24 weeks | 
| Tumor size reduction (2) | cCR (clinical complete remission) | 18 / 24 weeks | 
| Tumor size reduction (3) | measured by ultrasound (% reduction in therapy) | 18 / 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proliferation rate of the tumor cells | Ki67 protein analysis | 18 / 24 weeks | 
| narrowing the invasion front of the tumors | ultrasound | 18 / 24 weeks | 
| macrophage density in the tumor | serum chemistry | 18 / 24 weeks | 
| vascularization of the tumor | ultrasound | 18 / 24 weeks | 
| tolerability of chemotherapy | % reduction in therapy | 18 / 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, neoadjuvant chemotherapy, ultrasound, microbubbles