KVUS at Neoadjuvant CTx of Breast Cancer

Contrast-enhanced Ultrasound in Neoadjuvant Chemotherapy of Breast Cancer

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

Study Overview

• Status: Unknown
• Conditions: Early Primary Breast Cancer
• Intervention / Treatment: Drug: SonoVue

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 Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany
    • Recruiting
    • Department of Gynecology and Obstetrics
    • Contact: Elmar Stickeler, Univ.-Prof. Dr. med.; Phone Number: +49 241 80 88400; Email: estickeler@ukaachen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: A; Application and measurement of tumor size using contrast agent-enhanced diagnostic and therapy supporting (with SonoVue®) ultrasound	Drug: SonoVue; As part of the study therapy supportive ultrasound will be performed with iv Infusion of the chemotherapeutic agent.
NO_INTERVENTION: B; Application and measurement of tumor size using contrast agent-enhanced diagnostic ultrasound

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor size reduction (1)	pCR (pathohistological complete remission)	18 / 24 weeks
Tumor size reduction (2)	cCR (clinical complete remission)	18 / 24 weeks
Tumor size reduction (3)	measured by ultrasound (% reduction in therapy)	18 / 24 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: RWTH Aachen University
• Collaborators: Univ.-Prof. Dr. med. F. Kiessling
• Investigators: Principal Investigator: Elmar Stickeler, niv.-Prof. Dr. med., Department of Gynecology and Obstetrics

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 12, 2016
• Primary Completion (ANTICIPATED): June 12, 2019
• Study Completion (ANTICIPATED): December 12, 2019

Study Registration Dates

• First Submitted: December 19, 2017
• First Submitted That Met QC Criteria: December 27, 2017
• First Posted (ACTUAL): December 28, 2017

Study Record Updates

• Last Update Posted (ACTUAL): December 28, 2017
• Last Update Submitted That Met QC Criteria: December 27, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: breast cancer, neoadjuvant chemotherapy, ultrasound, microbubbles
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 16-134

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The study results will be published in at least one scientific article.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No