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

March 25, 2024 updated by: Kibo Nam
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.

Study Overview

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University Hospital
        • Contact:
        • Principal Investigator:
          • Kibo Nam, PhD
    • Texas
      • Dallas, Texas, United States, 75390

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Diagnostic (CEUS, Definity)
Patients undergo CEUS and receive perflutren lipid microspheres IV over 10-15 minutes before NAC, after 10% of NAC, and after 30% of NAC
Undergo CEUS
Other Names:
  • CEUS
Given IV
Other Names:
  • Definity

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Calculation of tumor volume changes with neoadjuvant chemotherapy (NAC)
Time Frame: Up to study completion (48 months)
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)
Prediction of the patients' clinical and pathological response
Time Frame: Up to study completion (48 months)
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)
The ability of the SHAPE method to distinguish responders from non-responders
Time Frame: Up to study completion (48 months)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Accuracy of the 3D SHAPE for predicting locally advanced breast cancer NAC response varies with breast cancer subtype
Time Frame: Up to study completion (48 months)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 7, 2020

Primary Completion (Estimated)

May 31, 2026

Study Completion (Estimated)

May 31, 2026

Study Registration Dates

First Submitted

January 14, 2021

First Submitted That Met QC Criteria

January 19, 2021

First Posted (Actual)

January 20, 2021

Study Record Updates

Last Update Posted (Actual)

March 27, 2024

Last Update Submitted That Met QC Criteria

March 25, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Other Study ID Numbers

  • 20F.259
  • R37CA234428 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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