Early Primary Breast Cancer
Conditions
Keywords
breast cancer, neoadjuvant chemotherapy, ultrasound, microbubbles
Brief summary
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
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.
Interventions
DRUGSonoVue
As part of the study therapy supportive ultrasound will be performed with iv Infusion of the chemotherapeutic agent.
Sponsors
Univ.-Prof. Dr. med. F. Kiessling
RWTH Aachen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Parellel Assignment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor size reduction (1) | 18 / 24 weeks | pCR (pathohistological complete remission) |
| Tumor size reduction (2) | 18 / 24 weeks | cCR (clinical complete remission) |
| Tumor size reduction (3) | 18 / 24 weeks | measured by ultrasound (% reduction in therapy) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| vascularization of the tumor | 18 / 24 weeks | ultrasound |
| proliferation rate of the tumor cells | 18 / 24 weeks | Ki67 protein analysis |
| tolerability of chemotherapy | 18 / 24 weeks | % reduction in therapy |
| narrowing the invasion front of the tumors | 18 / 24 weeks | ultrasound |
| macrophage density in the tumor | 18 / 24 weeks | serum chemistry |
Countries
Germany
Contacts
Primary ContactElmar Stickeler, Univ.-Prof. Dr. med.
Backup ContactFabian Kiessling, Univ.-Prof. Dr. med.
Outcome results
None listed