search
Back to results

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

Primary Purpose

Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Contrast-Enhanced Ultrasound
Perflutren Lipid Microspheres
Sponsored by
Kibo Nam
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Anatomic Stage III Breast Cancer AJCC v8

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Thomas Jefferson University HospitalRecruiting
  • UT Southwestern/Simmons Cancer Center-DallasRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Diagnostic (CEUS, Definity)

Arm Description

Patients undergo CEUS and receive perflutren lipid microspheres IV over 10-15 minutes before NAC, after 10% of NAC, and after 30% of NAC

Outcomes

Primary Outcome Measures

Prediction of the patients' clinical and pathological response
The SHAPE results from three time points will be compared to the patients' clinical response as well as pathological response. The imaging response outcome will be determined by the tumor size reduction percentage. We will use a threshold value of 90% to differentiate the responders from partial/non-responders. MRI baseline images before and after the completion of the NAC will be acquired if available. If a patient's MRIs are not available, 3D measurements from ultrasound images will be utilized. A subject who drops out of the study during the therapy, due to the progression of disease, will be considered as a non-responder. The pathologic response will be evaluated with a 5-point grading scale: no therapeutic effect (grade 1), minimal therapeutic effect (grade 2), moderated therapeutic effect with invasive tumor or vascular invasion (grade 3), marked therapeutic effect with no/minimal invasive tumor (grade 4), or complete therapeutic effect with no invasive disease (grade 5).

Secondary Outcome Measures

Comparison of prediction accuracy of SHAPE based on breast cancer subtype
The accuracy of SHAPE to predict the patients' clinical and pathological outcomes will be compared among breast cancer subtypes. We will determine the patients' clinical and pathological outcomes in the same way for the primary outcome measure. Based on the collected tumor information after surgery, ER, PR, HER2 and ki-67 will be used to divide breast cancers treated with NAC into 4 subtypes: luminal A (ER+, PR+, HER2-, and ki-67≤14%), luminal B (ER+, PR+, HER2- and ki-67>14%; ER+ and/or PR+, HER2+), HER2-overexpression (ER-, PR- and HER2+) and triple-negative (ER-, PR-, and HER2-). The ability of the SHAPE method to distinguish responders from non-responders will be compared between breast cancer subtypes using ROC analysis.

Full Information

First Posted
January 14, 2021
Last Updated
February 8, 2023
Sponsor
Kibo Nam
search

1. Study Identification

Unique Protocol Identification Number
NCT04715958
Brief Title
Monitoring Neoadjuvant Chemotherapy of Breast Cancer Using 3D Subharmonic Aided Pressure Estimation
Official Title
Monitoring Neoadjuvant Chemotherapy of Breast Cancer Using 3D Subharmonic Aided Pressure Estimation
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 7, 2020 (Actual)
Primary Completion Date
January 1, 2024 (Anticipated)
Study Completion Date
April 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Kibo Nam

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II/III trial studies if contrast-enhanced ultrasound (CEUS) using a contrast agent, perflutren lipid microspheres (Definity), can predict the early response of breast cancer to neoadjuvant chemotherapy by estimating the pressure gradient between the breast cancer and surrounding tissues. To estimate the pressures noninvasively, subharmonic (half of fundamental frequency) aided pressure estimation (SHAPE) using CEUS will be utilized. The study hypothesis is that the subharmonic signal difference in the tumor relative to the normal tissue can predict breast cancer NAC response after 10% of therapy regimen.
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 NAC response varies with breast cancer subtype. OUTLINE: Patients undergo contrast-enhanced ultrasound (CEUS) with Definity (perflutren lipid microspheres) intravenously (IV) over 10-15 minutes before NAC, after 10% (1-2 cycles) of NAC, and after 30% (2-4 cycles) of NAC. After completion of study, patients are followed up at the completion of NAC.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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, 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

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Diagnostic (CEUS, Definity)
Arm Type
Experimental
Arm Description
Patients undergo CEUS and receive perflutren lipid microspheres IV over 10-15 minutes before NAC, after 10% of NAC, and after 30% of NAC
Intervention Type
Procedure
Intervention Name(s)
Contrast-Enhanced Ultrasound
Other Intervention Name(s)
CEUS
Intervention Description
Undergo CEUS
Intervention Type
Drug
Intervention Name(s)
Perflutren Lipid Microspheres
Other Intervention Name(s)
Definity
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Prediction of the patients' clinical and pathological response
Description
The SHAPE results from three time points will be compared to the patients' clinical response as well as pathological response. The imaging response outcome will be determined by the tumor size reduction percentage. We will use a threshold value of 90% to differentiate the responders from partial/non-responders. MRI baseline images before and after the completion of the NAC will be acquired if available. If a patient's MRIs are not available, 3D measurements from ultrasound images will be utilized. A subject who drops out of the study during the therapy, due to the progression of disease, will be considered as a non-responder. The pathologic response will be evaluated with a 5-point grading scale: no therapeutic effect (grade 1), minimal therapeutic effect (grade 2), moderated therapeutic effect with invasive tumor or vascular invasion (grade 3), marked therapeutic effect with no/minimal invasive tumor (grade 4), or complete therapeutic effect with no invasive disease (grade 5).
Time Frame
Up to study completion (48 months)
Secondary Outcome Measure Information:
Title
Comparison of prediction accuracy of SHAPE based on breast cancer subtype
Description
The accuracy of SHAPE to predict the patients' clinical and pathological outcomes will be compared among breast cancer subtypes. We will determine the patients' clinical and pathological outcomes in the same way for the primary outcome measure. Based on the collected tumor information after surgery, ER, PR, HER2 and ki-67 will be used to divide breast cancers treated with NAC into 4 subtypes: luminal A (ER+, PR+, HER2-, and ki-67≤14%), luminal B (ER+, PR+, HER2- and ki-67>14%; ER+ and/or PR+, HER2+), HER2-overexpression (ER-, PR- and HER2+) and triple-negative (ER-, PR-, and HER2-). The ability of the SHAPE method to distinguish responders from non-responders will be compared between breast cancer subtypes using ROC analysis.
Time Frame
Up to study completion (48 months)

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kibo Nam, PhD
Phone
215-955-6261
Email
Kibo.Nam@jefferson.edu
First Name & Middle Initial & Last Name & Degree
Kibo Nam, PhD
Facility Name
UT Southwestern/Simmons Cancer Center-Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Basak Dogan
Phone
214-645-9729
Email
Basak.dogan@utsouthwestern.edu

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs