KVUS at Neoadjuvant CTx of Breast Cancer

Phase 3

• Conditions: Early Primary Breast Cancer
• Interventions: Drug: SonoVue

• Registration Number: NCT03385200
• Lead Sponsor: RWTH Aachen University

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.

Study Timeline

• Study Start: 2016-12-12
• Status Verified: 2017-12
• Study First Submitted: 2017-12-19
• Study First Submitted QC: 2017-12-27
• Last Update Submitted: 2017-12-27
• Study First Posted: 2017-12-28
• Last Update Posted: 2017-12-28
• Primary Completion: 2019-06-12
• Study Completion: 2019-12-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	SonoVue	Application and measurement of tumor size using contrast agent-enhanced diagnostic and therapy supporting (with SonoVue®) ultrasound

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
proliferation rate of the tumor cells	18 / 24 weeks	Ki67 protein analysis
narrowing the invasion front of the tumors	18 / 24 weeks	ultrasound
macrophage density in the tumor	18 / 24 weeks	serum chemistry
vascularization of the tumor	18 / 24 weeks	ultrasound
tolerability of chemotherapy	18 / 24 weeks	% reduction in therapy

Trial Locations

Locations (1)

Department of Gynecology and Obstetrics; 🇩🇪 Aachen, Germany