Effect of the contrast-enhanced diagnostic ultrasound during neoadjuvant chemotherapy of breast cancer on the achieved tumor size reduction and tolerability of chemotherapy
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
As part of the study therapy supportive ultrasound will be performed with iv Infusion of the chemotherapeutic agent.
Department of Gynecology and Obstetrics
Aachen, Germany
RECRUITINGTumor size reduction (1)
pCR (pathohistological complete remission)
Time frame: 18 / 24 weeks
Tumor size reduction (2)
cCR (clinical complete remission)
Time frame: 18 / 24 weeks
Tumor size reduction (3)
measured by ultrasound (% reduction in therapy)
Time frame: 18 / 24 weeks
proliferation rate of the tumor cells
Ki67 protein analysis
Time frame: 18 / 24 weeks
narrowing the invasion front of the tumors
ultrasound
Time frame: 18 / 24 weeks
macrophage density in the tumor
serum chemistry
Time frame: 18 / 24 weeks
vascularization of the tumor
ultrasound
Time frame: 18 / 24 weeks
tolerability of chemotherapy
% reduction in therapy
Time frame: 18 / 24 weeks
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