KVUS at Neoadjuvant CTx of Breast Cancer

Early Primary Breast Cancer Clinical Trial

Official title:

Contrast-enhanced Ultrasound in Neoadjuvant Chemotherapy of Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03385200
• Other study ID #: 16-134
• Status: Recruiting
• Phase: Phase 3
• First received: December 19, 2017
• Last updated: December 27, 2017
• Start date: December 12, 2016
• Est. completion date: December 12, 2019

Study information

• Verified date: December 2017
• Source: RWTH Aachen University
• Contact: Elmar Stickeler, Univ.-Prof. Dr. med.
• Phone: +49 241 80 88400
• Email: estickeler[@]ukaachen.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 12, 2019
• Est. primary completion date: June 12, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Early Primary Breast Cancer

Intervention

Drug:
• SonoVue
As part of the study therapy supportive ultrasound will be performed with iv Infusion of the chemotherapeutic agent.

Locations

Country	Name	City	State
Germany	Department of Gynecology and Obstetrics	Aachen

Sponsors (2)

Lead Sponsor	Collaborator
RWTH Aachen University	Univ.-Prof. Dr. med. F. Kiessling

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor size reduction (1)	pCR (pathohistological complete remission)	18 / 24 weeks
Primary	Tumor size reduction (2)	cCR (clinical complete remission)	18 / 24 weeks
Primary	Tumor size reduction (3)	measured by ultrasound (% reduction in therapy)	18 / 24 weeks
Secondary	proliferation rate of the tumor cells	Ki67 protein analysis	18 / 24 weeks
Secondary	narrowing the invasion front of the tumors	ultrasound	18 / 24 weeks
Secondary	macrophage density in the tumor	serum chemistry	18 / 24 weeks
Secondary	vascularization of the tumor	ultrasound	18 / 24 weeks
Secondary	tolerability of chemotherapy	% reduction in therapy	18 / 24 weeks