mULM to Support Breast Cancer Diagnosis and Therapy

Primary Breast Cancer Clinical Trial

Official title:

Development of Motion-Model Ultrasound Localization Microscopy to Support Breast Cancer Diagnosis and Therapy Monitoring in Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05445050
• Other study ID #: 351-19
• Secondary ID: DRKS00023954
• Status: Recruiting
• Phase: N/A
• Start date: April 26, 2021
• Est. completion date: October 1, 2024

Study information

• Verified date: November 2023
• Source: RWTH Aachen University
• Contact: Elmar Stickeler, Prof Dr. med
• Phone: +492418088400
• Email: estickeler[@]ukaachen.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this project is to adapt the super-resolution ultrasound imaging technology motion-model Ultrasound Localization Microscopy (mULM) to clinical application. In this exploratory patient study a scan protocol will be established to subsequently investigate whether mULM allows the assessment of the tumor response to neoadjuvant chemotherapy in participants with a primary breast cancer diagnosis as well as for the differentiation of benign and malignant breast tumors in participants with lesions of unknown dignity.

Description:

This study on the clinical translation of the super-resolution ultrasound imaging technique motion-model ultrasound localization microscopy (mULM) is composed of three parts. First, an ultrasound scan protocol will be developed by providing patients with primary breast carcinoma with an ultrasound scan to assess the size, location, and structure of the tumor. Images in the form of B-mode ultrasound, elastography, and contrast ultrasound will be obtained, and mini-movies of the CEUS examinations will be evaluated in a post-processing step. There, individual microbubbles of the ultrasound contrast agent will be identified and tracked to reconstruct the microvasculature of the tumor lesions. Participants will each receive 2 different doses of the clinically approved ultrasound contrast agent SonoVue®. The morphological and functional parameters obtained through the post-processing with the mULM algorithm are then analyzed and subsequently validated with histological examinations. Finally, the ultrasound examination protocol will be optimized and the corresponding dosage of the ultrasound contrast agent determined. The examination protocol established in the first section will subsequently be applied to patients with primary breast carcinoma receiving neoadjuvant chemotherapy. Contrast-enhanced ultrasonography will be performed at three time points during the chemotherapy cycles and will be performed to assess tumor perfusion through application of the mULM-algorithm. The dosage of contrast agent is based on the dosage found in the previous part of the study. The CEUS examination is followed by the infusion of the chemotherapeutic agent. After completion of neoadjuvant chemotherapy, surgical resection of the tumor and microscopic examination of the tissue are performed according to guidelines. In the final part of the study, patients with suspected breast tumor lesions are examined. They will first receive non-contrast-enhanced diagnostic ultrasound (B-mode and elastography). A contrast-enhanced ultrasound examination is performed on the largest lesion. To further develop the mULM methodology, this is performed as both 2D and 3D acquisition. The dosage of the contrast agent examination is again based on the optimal dosage found in the first study part. This ultrasound procedure is followed by guideline-guided biopsy for histologic clarification of the tumors, assessing dignity, hormone receptor as well as and HER2/neu status, proliferation rate, and vessel density.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 74
• Est. completion date: October 1, 2024
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• written informed consent
• age = 18 yrs
• histologically confirmed primary breast cancer including all intrinsic subtypes (study parts A and B)
• highly suspected primary breast cancer (study part C)
• treatment with neoadjuvant chemotherapy (study part B)
• persons who are legally competent and mentally able to follow the instructions of the study team

Exclusion Criteria:

• younger than 18 years
• hypersensitivity / allergy to sulfur hexafluoride, Macrogol 4000, distearoylphosphatidylcholine, dipalmitoylphosphatidylglycerol-sodium, palmitic acid
• right-left shunt,
• signs of cardiovascular instability
• acute endocarditis
• artificial heart valves
• acute systemic inflammation and/or sepsis
• overactive coagulation status and/or recent thromboembolic events
• end stage of liver and kidney diseases
• 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
• Primary Breast Cancer

Intervention

Diagnostic Test:
• Application and measurement of tumor vascularization using diagnostic contrast enhanced ultrasound (CEUS)
Part A: performing CEUS with the contrast agent SonoVue® at two different doses and two different injection speeds in participants with primary breast cancer Part B: performing CEUS with the contrast agent SonoVue® using the established protocol from part A in participants undergoing neoadjuvant chemotherapy Part C: performing CEUS with the contrast agent SonoVue® using the established protocol from part A in participants with lesions of unknown dignity

Locations

Country	Name	City	State
Germany	Department of Gynecology and Obstetrics Universitätsklinikum Aachen, AöR	Aachen	NRW

Sponsors (1)

Lead Sponsor	Collaborator
RWTH Aachen University

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relative blood volume	Relative blood volume in % - describes the degree of vascularization - measured with mULM	Study Part A & C: approximately 1 day before surgical removal of tumor
Primary	Blood flow	Blood flow in mm/s - measured with mULM	Study Part A & C: approximately 1 day before surgical removal of tumor
Primary	Change of relative blood volume	Change of relative blood volume in %	Study Part B: at the beginning of (approximately 1 hour before) first, second and fourth cycle of neoadjuvant chemotherapeutic treatment (each cycle is 14 days)
Primary	Change of blood flow	Change of blood flow in mm/s	Study Part B: at the beginning of (approximately 1 hour before) first, second and fourth cycle of neoadjuvant chemotherapeutic treatment (each cycle is 14 days)
Secondary	Change of tumor size	Change of tumor size determined based on ultrasound B-mode imaging	Study Part B: at the beginning of (approximately 1 hour before) first, second and fourth cycle of neoadjuvant chemotherapeutic treatment (each cycle is 14 days)