Clinical trial NCT03385200: KVUS at Neoadjuvant CTx of Breast Cancer
Official title: Contrast-enhanced Ultrasound in Neoadjuvant Chemotherapy of Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Early Primary Breast Cancer
Keywords: breast cancer, neoadjuvant chemotherapy, ultrasound, microbubbles
Lead sponsor: RWTH Aachen University
Sponsor class: OTHER
Collaborators: name: Univ.-Prof. Dr. med. F. Kiessling
First posted: 2017-12-28
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parellel Assignment
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Tumor size reduction (1)
timeFrame: 18 / 24 weeks
measure: Tumor size reduction (2)
timeFrame: 18 / 24 weeks
measure: Tumor size reduction (3)
timeFrame: 18 / 24 weeks
Secondary outcomes:
measure: proliferation rate of the tumor cells
timeFrame: 18 / 24 weeks
measure: narrowing the invasion front of the tumors
timeFrame: 18 / 24 weeks
measure: macrophage density in the tumor
timeFrame: 18 / 24 weeks
measure: vascularization of the tumor
timeFrame: 18 / 24 weeks
measure: tolerability of chemotherapy
timeFrame: 18 / 24 weeks
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Department of Gynecology and Obstetrics
Study officials:
affiliation: Department of Gynecology and Obstetrics
name: Elmar Stickeler, niv.-Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: