Monitoring Neoadjuvant Chemotherapy of Breast Cancer Using 3D Subharmonic Aided Pressure Estimation

Anatomic Stage III Breast Cancer AJCC v8 Clinical Trial

Official title:

Monitoring Neoadjuvant Chemotherapy of Breast Cancer Using 3D Subharmonic Aided Pressure Estimation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04715958
• Other study ID #: 20F.259
• Secondary ID: R37CA234428
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: December 7, 2020
• Est. completion date: May 31, 2026

Study information

• Verified date: March 2024
• Source: Thomas Jefferson University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II/III trial studies if contrast-enhanced ultrasounds using a contrast dye, perflutren lipid microspheres (Definity), can predict the response to chemotherapy by estimating the pressure in the cancer in patients with breast cancer that has spread to nearby tissues and lymph nodes (locally advanced). The efficacy of cancer therapy is affected by the pressure in the cancer. Definity is a contrast dye used to create better images during ultrasounds. The purpose of this trial is to determine if a special kind of ultrasound, called contrast-enhanced ultrasound, an experimental imaging test, can detect pressures in cancer to determine the response to neoadjuvant chemotherapy in patients with breast cancer.

Description:

PRIMARY OBJECTIVE:

I. To apply and evaluate a novel biomarker from 3-dimensional subharmonic aided pressure estimation (3D SHAPE) to predict neoadjuvant chemotherapy (NAC) response in patients with breast cancer.

SECONDARY OBJECTIVE:

I. To assess whether the accuracy of 3D SHAPE for predicting locally advanced breast cancer (LABC) NAC response varies with breast cancer subtype.

OUTLINE:

Patients undergo contrast-enhanced ultrasound (CEUS) and receive perflutren lipid microspheres intravenously (IV) over 10-15 minutes before NAC, after 10% of NAC, and after 30% of NAC. Patients also undergo unenhanced baseline ultrasound imaging before NAC, after 10% of NAC, after 30% of NAC, and after 100% of NAC.

After completion of study, patients are followed up at the completion of NAC.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: May 31, 2026
• Est. primary completion date: May 31, 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

• Provide signed and dated informed consent form

• Willing to comply with all study procedures and be available for the duration of the study

• At least 21 years old

• Be diagnosed with breast cancer (T1 or greater LABC, any N and M0)

• Be scheduled for neoadjuvant chemotherapy

• Be medically stable

• Be conscious and able to comply with study procedures

• If a female of child-bearing potential, must have a negative urine pregnancy test

Exclusion Criteria:

• Females who are pregnant or nursing

• Patients with other primary cancers requiring systemic treatment

• Patients with any distal metastatic disease

• Patients undergoing neoadjuvant endocrine therapy

• Patients who are medically unstable, patients who are seriously or terminally ill, and patients whose clinical course is unpredictable. For example:

• Patients on life support or in a critical care unit;

• Patients with unstable occlusive disease (e.g., crescendo angina);

• Patients with clinically unstable cardiac arrhythmias, such as recurrent ventricular tachycardia;

• Patients with uncontrolled congestive heart failure (New York Heart Association [NYHA] Class IV);

• Patients with recent cerebral hemorrhage;

• Patients who have undergone surgery within 24 hours prior to the study sonographic examination

• Patients with known hypersensitivity or allergy to any component of Definity

• Patients with unstable cardiopulmonary conditions or respiratory distress syndrome

• Patients with uncontrollable emphysema, pulmonary vasculitis, pulmonary hypertension or a history of pulmonary emboli

Related Conditions & MeSH terms

• Anatomic Stage III Breast Cancer AJCC v8
• Anatomic Stage IIIA Breast Cancer AJCC v8
• Anatomic Stage IIIB Breast Cancer AJCC v8
• Anatomic Stage IIIC Breast Cancer AJCC v8
• Breast Neoplasms
• Locally Advanced Breast Carcinoma
• Prognostic Stage III Breast Cancer AJCC v8
• Prognostic Stage IIIA Breast Cancer AJCC v8
• Prognostic Stage IIIB Breast Cancer AJCC v8
• Prognostic Stage IIIC Breast Cancer AJCC v8

Intervention

Procedure:
• Contrast-Enhanced Ultrasound
Undergo CEUS

Drug:
• Perflutren Lipid Microspheres
Given IV

Locations

Country	Name	City	State
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Kibo Nam	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Calculation of tumor volume changes with neoadjuvant chemotherapy (NAC)	3-dimensional (3D) tumor measurements over the three ultrasound exams will be recorded for each subject to calculate tumor volume changes with NAC. The tumor volume change during the therapy will be compared to imaging (magnetic resonance imaging or ultrasound) and pathologic response as well as to the corresponding 3D subharmonic aided pressure estimation (SHAPE) results.	Up to study completion (48 months)
Primary	Prediction of the patients' clinical and pathological response	The SHAPE results from three time points (i.e. before, 10% completion, and 30% completion of NAC) will be modeled for predicting the patients' clinical response as well as pathological response using longitudinal logistic regression with adjustment for correlated observations over time by generalized linear mixed effects or generalized estimating equations (GEE) modeling.	Up to study completion (48 months)
Primary	The ability of the SHAPE method to distinguish responders from non-responders	Will also be compared using receiver operating characteristic analysis to develop thresholds for decision-making based on balancing sensitivity and specificity.	Up to study completion (48 months)
Secondary	Accuracy of the 3D SHAPE for predicting locally advanced breast cancer NAC response varies with breast cancer subtype	The variation of the accuracies of the SHAPE results by breast cancer subtypes will be reported. The generalized linear mixed effects or GEE modeling will be stratified by breast cancer subtype and also extended to include modeling of breast cancer subtype as a main effect and as an interaction effect with SHAPE.	Up to study completion (48 months)