Breast Cancer
Conditions
Keywords
Breast cancer, Interstitial fluid pressure, Angiogenesis, Contrast enhanced ultrasound imaging, Subharmonic imaging, Subharmonic pressure estimation
Brief summary
This is a diagnostic accuracy study to evaluate if two novel ultrasound (US) techniques, quantitative 3D subharmonic imaging (SHI) and Subharmonic Aided Pressure Estimation (SHAPE), used with an intravenous ultrasound contrast agent (Definity, Lantheus Medical Imaging, Billerica, MA), can track changes in locally advanced breast cancer (LABC) angiogenesis and interstitial fluid pressure (IFP), respectively, by studying women undergoing neoadjuvant chemotherapy before as well as with around 10% and 60% (in part 1) or 30% (in part 2) of the neoadjuvant chemotherapy treatment delivered and after completion of the neoadjuvant chemotherapy treatment. Results will be compared to MRI and pathology.
Interventions
DRUGDefinity infusion
3 ml of Perflutren Lipid Microspheres (Definity) mixed in 50 ml of saline is infused at a rate of approximately 4ml/min
Sponsors
U.S. Army Medical Research and Development Command
Sidney Kimmel Cancer Center at Thomas Jefferson University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Females * Be diagnosed with T1 or greater LABC, any N and M0. * Be scheduled for neoadjuvant chemotherapy * Be at least 21 years of age. * Be medically stable. * If a female of child-bearing potential, must have a negative pregnancy test. * Have signed Informed Consent to participate in the study.
Exclusion criteria
* Males * Females who are pregnant or nursing. * Patients with other primary cancers requiring systemic treatment. * Patients with any metastatic disease. * Patients undergoing neoadjuvant endocrine therapy. * Patients with known hypersensitivity or allergy to any component of Definity. * Patients with cardiac shunts or congenital heart defects. * Patients with unstable cardiopulmonary conditions or respiratory distress syndrome. * Patients with uncontrollable emphysema, pulmonary vasculitis, pulmonary hypertension or a history of pulmonary emboli. * Patients who have received any contrast medium (X-ray, MRI, CT or US) in the 24 hours prior to the research US exam.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subharmonic Aided Pressure Estimation (SHAPE) After Treatment for Complete Responders | from baseline to completion of neoadjuvant chemotherapy, average of 6 months | To evaluate the ability of SHAPE, used with Definity, to track changes in interstitial fluid pressure (IFP) by studying women undergoing neoadjuvant chemotherapy before as well as with around 10% and 30% of the neoadjuvant chemotherapy treatment delivered and comparing results to MRI and pathology. |
| Subharmonic Aided Pressure Estimation (SHAPE) After Treatment for Partial Responders | from baseline to completion of neoadjuvant chemotherapy | To evaluate the ability of SHAPE, used with Definity, to track changes in interstititial fluid (IFP) by studying women undergoing neoadjuvant chemotherapy before as well as with around 10% 30% of the neoadjuvant chemotherapy treatment delivered and after completion of the neoadjuvant chemotherapy treatment and comparing results to MRI and pathology. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subharmonic Imaging (SHI) Depiction of Breast Cancer Angiogenesis for Complete Responders | From baseline to after surgery | To compare the 3D Subharmonic imaging (SHI) depiction of breast cancer angiogenesis in humans to CD31, an immunohistochemical predictor of angiogenesis. |
| SHI Depiction of Breast Cancer Angiogenesis for Partial Responders | After surgery; on average 6 months | To compare the 3D SHI depiction of breast cancer angiogenesis in humans to CD31, an immunohistochemical predictor of angiogenesis. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Definity Infusion Infusion of Definity (Perflutren Lipid Microspheres)
Definity infusion: 3 ml of Perflutren Lipid Microspheres (Definity) mixed in 50 ml of saline is infused at a rate of approximately 4ml/min | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Definity Infusion |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 17 participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 17 |
| other Total, other adverse events | 0 / 17 |
| serious Total, serious adverse events | 0 / 17 |
Outcome results
Primary
Subharmonic Aided Pressure Estimation (SHAPE) After Treatment for Complete Responders
To evaluate the ability of SHAPE, used with Definity, to track changes in interstitial fluid pressure (IFP) by studying women undergoing neoadjuvant chemotherapy before as well as with around 10% and 30% of the neoadjuvant chemotherapy treatment delivered and comparing results to MRI and pathology.
Time frame: from baseline to completion of neoadjuvant chemotherapy, average of 6 months
Population: six participants were not counted in the data analysis. 2 due to technical issues, 2 withdrew due to worsening of underlying disease, and 2 stopped their nedoadjuvant chemotherapy treatment unexpectedly. Data presented below is for those who achieved Complete Response (CR)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Definity Infusion | Subharmonic Aided Pressure Estimation (SHAPE) After Treatment for Complete Responders | 10% completion of neoadjuvant chemotherapy for | 3.23 dB | Standard Deviation 1.41 |
| Definity Infusion | Subharmonic Aided Pressure Estimation (SHAPE) After Treatment for Complete Responders | 30% completion of neoadjuvant chemotherapy | 1.67 dB | Standard Deviation 1.09 |
Primary
Subharmonic Aided Pressure Estimation (SHAPE) After Treatment for Partial Responders
To evaluate the ability of SHAPE, used with Definity, to track changes in interstititial fluid (IFP) by studying women undergoing neoadjuvant chemotherapy before as well as with around 10% 30% of the neoadjuvant chemotherapy treatment delivered and after completion of the neoadjuvant chemotherapy treatment and comparing results to MRI and pathology.
Time frame: from baseline to completion of neoadjuvant chemotherapy
Population: six participants were not counted in the data analysis. 2 due to technical issues, 2 withdrew due to worsening of underlying disease, and 2 stopped their nedoadjuvant chemotherapy treatment unexpectedly. Data presented below is for those who achieved Partial Response (PR)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Definity Infusion | Subharmonic Aided Pressure Estimation (SHAPE) After Treatment for Partial Responders | 10% completion of neoadjuvant chemotherapy for | -0.88 dB | Standard Deviation 1.46 |
| Definity Infusion | Subharmonic Aided Pressure Estimation (SHAPE) After Treatment for Partial Responders | 30% completion of neoadjuvant chemotherapy | 0.06 dB | Standard Deviation 0.9 |
Secondary
SHI Depiction of Breast Cancer Angiogenesis for Partial Responders
To compare the 3D SHI depiction of breast cancer angiogenesis in humans to CD31, an immunohistochemical predictor of angiogenesis.
Time frame: After surgery; on average 6 months
Population: Data presented below is for those who achieved Partial Response (PR)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Definity Infusion | SHI Depiction of Breast Cancer Angiogenesis for Partial Responders | 0 dB | Standard Deviation 1.2 |
Secondary
Subharmonic Imaging (SHI) Depiction of Breast Cancer Angiogenesis for Complete Responders
To compare the 3D Subharmonic imaging (SHI) depiction of breast cancer angiogenesis in humans to CD31, an immunohistochemical predictor of angiogenesis.
Time frame: From baseline to after surgery
Population: six participants were not counted in the data analysis. 2 due to technical issues, 2 withdrew due to worsening of underlying disease, and 2 stopped their nedoadjuvant chemotherapy treatment unexpectedly. Data presented below is for those who achieved Complete Response (CR)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Definity Infusion | Subharmonic Imaging (SHI) Depiction of Breast Cancer Angiogenesis for Complete Responders | 1.1 dB | Standard Deviation 1.9 |