Monitoring Neoadjuvant Chemotherapy of Breast Cancer Using 3D Subharmonic Aided Pressure Estimation
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
|
Phase 2/Phase 3 |
Detailed Description
PRIMARY OBJECTIVE:
- 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:
- 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.
Study Design
Arms and Interventions
| 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 |
Procedure: Contrast-Enhanced Ultrasound
Undergo CEUS
Other Names:
Drug: Perflutren Lipid Microspheres
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Prediction of the patients' clinical and pathological response [Up to study completion (48 months)]
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 [Up to study completion (48 months)]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Provide signed and dated informed consent form
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Willing to comply with all study procedures and be available for the duration of the study
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At least 21 years old
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Be diagnosed with breast cancer (T1 or greater LABC, any N and M0)
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Be scheduled for neoadjuvant chemotherapy
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Be medically stable
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Be conscious and able to comply with study procedures
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If a female of child-bearing potential, must have a negative urine pregnancy test
Exclusion Criteria:
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Females who are pregnant or nursing
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Patients with other primary cancers requiring systemic treatment
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Patients with any distal metastatic disease
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Patients undergoing neoadjuvant endocrine therapy
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Patients who are medically unstable, patients who are seriously or terminally ill, and patients whose clinical course is unpredictable. For example:
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Patients on life support or in a critical care unit;
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Patients with unstable occlusive disease (e.g., crescendo angina);
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Patients with clinically unstable cardiac arrhythmias, such as recurrent ventricular tachycardia;
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Patients with uncontrolled congestive heart failure (New York Heart Association [NYHA] Class IV);
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Patients with recent cerebral hemorrhage;
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Patients who have undergone surgery within 24 hours prior to the study sonographic examination
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Patients with known hypersensitivity or allergy to any component of Definity
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Patients with unstable cardiopulmonary conditions or respiratory distress syndrome
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Patients with uncontrollable emphysema, pulmonary vasculitis, pulmonary hypertension or a history of pulmonary emboli
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Thomas Jefferson University Hospital | Philadelphia | Pennsylvania | United States | 19107 |
Sponsors and Collaborators
- Kibo Nam
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 20F.259