Clinical trial NCT05445050: mULM to Support Breast Cancer Diagnosis and Therapy
Official title: Development of Motion-Model Ultrasound Localization Microscopy to Support Breast Cancer Diagnosis and Therapy Monitoring in Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Primary Breast Cancer
Keywords: breast cancer
neoadjuvant chemotherapy
ultrasound
microbubbles
Lead sponsor: RWTH Aachen University
Sponsor class: OTHER
First posted: 2022-07-06
Enrollment: 74
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Relative blood volume
timeFrame: Study Part A & C: approximately 1 day before surgical removal of tumor
measure: Blood flow
timeFrame: Study Part A & C: approximately 1 day before surgical removal of tumor
measure: Change of relative blood volume
timeFrame: 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)
measure: Change of blood flow
timeFrame: 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 outcomes:
measure: Change of tumor size
timeFrame: 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)
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Department of Gynecology and Obstetrics Universitätsklinikum Aachen, AöR
state: NRW
Study officials:
affiliation: RWTH Aachen University Hospital
name: Elmar Stickeler, Prof Dr. med
role: PRINCIPAL_INVESTIGATOR
References: