Breast CancerPhase 2NCT04136912
3-D Super Resolution Ultrasound Microvascular Imaging
A Phase 2 study testing Definity and Acoustic Angiography in people with Breast Cancer and Thyroid Cancer, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
Trial summary
This is a 3-arm single center study of 45 patients. These cohorts will include 15 breast patients scheduled to undergo a biopsy, and 15 thyroid patients scheduled to undergo fine needle aspiration, biopsy, or thyroidectomy that consent to undergo an acoustic angiography in conjunction with b-mode ultrasound prior to… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Breast Cancer, Thyroid Cancer
- What is being tested?
- Definity and Acoustic Angiography
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 26 May 2022to 1 Aug 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Able to provide informed consent
- Negative urine pregnancy test in women of child-bearing potential
- Women
- Patient had a diagnostic breast ultrasound study performed at UNC
- Scheduled for a core needle or surgical breast biopsy of at least one breast lesion that is 2 cm or less in size and 3 cm in depth from the skin surface
- Able to provide informed consent
- Negative urine pregnancy test in women of child-bearing potential
- BIRADS score of 4 or 5.
Who cannot join
- Institutionalized subject (prisoner or nursing home patient)
- Critically ill or medically unstable and whose critical course during the observation period would be unpredictable (e.g., chronic obstructive pulmonary disease (COPD)
- Known hypersensitivity to perflutren lipid (Definity®)
- Active cardiac disease including any of the following:
- Severe congestive heart failure
- Unstable angina.
Show all 39Show fewer
- Severe arrhythmia
- Myocardial infarction within 14 days prior to the date of proposed Definity® administration.
- Pulmonary hypertension
- Cardiac shunts
- Breast Imaging Patients
- Male
- Institutionalized subject (prisoner or nursing home patient)
- Critically ill or medically unstable and whose critical course during the observation period would be unpredictable (e.g., chronic obstructive pulmonary disease (COPD)
- Sonographically visible breast lesion larger than 2cm or greater than 3cm in depth from the skin surface
- Known hypersensitivity to perflutren lipid (Definity®)
- Active cardiac disease including any of the following:
- Severe congestive heart failure
- Unstable angina.
- Severe arrhythmia
- Myocardial infarction within 14 days prior to the date of proposed Definity® administration.
- Pulmonary hypertension
- Cardiac shunts
- Thyroid Imaging Patients Inclusion Criteria
- Patient had a diagnostic thyroid ultrasound study performed at UNC
- TIRADS risk score of 4c or 5
- Scheduled for a core needle or surgical thyroid biopsy, fine needle aspiration, or thyroidectomy of at least one sonographically visible thyroid lesion that is 3 cm in depth from the skin surface
- Able to provide informed consent
- Negative urine pregnancy test in women of child-bearing potential
- Institutionalized subject (prisoner or nursing home patient)
- Critically ill or medically unstable and whose critical course during the observation period would be unpredictable (e.g., chronic obstructive pulmonary disease (COPD)
- Known hypersensitivity to perflutren lipid (Definity®)
- Active cardiac disease including any of the following:
- Severe congestive heart failure
- Unstable angina.
- Severe arrhythmia
- Myocardial infarction within 14 days prior to the date of proposed Definity® administration.
- Pulmonary hypertension
- Cardiac shunts
Trial locations and contacts
1 site in 1 country.
United States1 site
Univeristy of North Carolina Chapel Hill
Chapel Hill, North Carolina, 27599
About this study
Official title: High Frame Rate 3-D Super Resolution Ultrasound Microvascular Imaging
This is a 3-arm single center study of 45 patients. These cohorts will include 15 breast patients scheduled to undergo a biopsy, and 15 thyroid patients scheduled to undergo fine needle aspiration, biopsy, or thyroidectomy that consent to undergo an acoustic angiography in conjunction with b-mode ultrasound prior to their scheduled biopsy. Prior to imaging clinical patients, the third arm will include 15 healthy volunteers that will be imaged to optimize imaging parameters.
Read the detailed description
Increasing the sensitivity and specificity of diagnostic imaging in patients at high risk for breast or thyroid cancer could provide substantial clinical benefit by improving diagnosis, preventing over-treatment, and reducing healthcare costs. Acoustic angiography is a new type of contrast enhanced ultrasound imaging which is specifically sensitive to microvascular structure and density. It evaluates tumor micro-vasculature and may provide a powerful prognostic tool for the diagnosis of breast cancer, and eventually for treatment evaluation.
- Conditions
- Breast Cancer, Thyroid Cancer
- Being tested
- Definity, Acoustic Angiography
- Keywords
- Cancer Screening
- Medical subject headings
- Breast Neoplasms, Thyroid Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DefinityDrug
Also called perflutren
Perflutren will be administered in split doses using the dosing range and administration type IV bolus) within the perflutren prescribing information. When administered as a bolus, the package insert recommends 10 uL/kg patient weight administered within 30-60 seconds, followed by a 10mL saline flush with a second dose of 10 uL/kg patient weight 30 minutes following the first dose, if needed.
Acoustic AngiographyDevice
Acoustic angiography imaging involves a research ultrasound scanner as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. Imaging will be performed within the package insert guidelines for ultrasound system mechanical index (a measurement of output power) when imaging perflutren contrast agent (less than 0.8).
Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Breast Imaging Cohort | Experimental | A total of 15 women with known breast lesions that are already scheduled to undergo a clinical biopsy Receives: Drug: Definity; Device: Acoustic Angiography |
| Thyroid Imaging Cohort | Experimental | A total of 15 participants with known thyroid lesions that are already scheduled to undergo a clinical biopsy Receives: Drug: Definity; Device: Acoustic Angiography |
| Healthy Volunteers Cohort | Experimental | A total of 15 participants will be included to optimize imaging parameters. Receives: Drug: Definity; Device: Acoustic Angiography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sensitivity of Acoustic Angiography; Breast Imaging
The sensitivity of Acoustic Angiography in the analysis of known breast lesions will be evaluated by comparing image analyses to the pathological results for these lesions.
Sensitivity (%) = True Positives (TP)+False Negatives (FN)True Positives (TP)
Measured: Baseline
Specificity of Acoustic Angiography; Breast Imaging (Percent of Negative Scans)
Specificity of Acoustic Angiography in the analysis of known breast lesions will be evaluated by comparing image analyses to the pathological results for these lesions. Specificity was calculated based on the formula, which is true negative / (true negative + false positive).
Measured: Baseline
Sensitivity of Acoustic Angiography; Thyroid Imaging (Percent of Positive Scans)
Sensitivity of Acoustic Angiography in the analysis of know thyroid lesions will be evaluated by comparing image analyses to the pathological results for these lesions. The study closed early due to insufficient funding and did not reach target enrollment. No participants were enrolled in Arm 2 (Thyroid Imaging); therefore, no outcome measure results are available.
Measured: Baseline
Specificity of Acoustic Angiography; Thyroid Imaging (Percent of Negative Scans)
Specificity of Acoustic Angiography in the analysis of known thyroid lesions will be evaluated by comparing image analyses to the pathological results for these lesions. The study closed early due to insufficient funding and did not reach target enrollment. No participants were enrolled in Arm 2 (Thyroid Imaging); therefore, no outcome measure results are available.
Measured: Baseline
Secondary outcomes (6)
Area Under the Curve of Acoustic Angiography (Arbitrary Units)
To compare the area under the curve (AUC) of acoustic angiography to the AUC of the B-mode ultrasound. Readers assigned a malignancy likelihood score from 1 to 5, with 1 likely benign to 5 likely malignant. An AUC was then calculated based on these scores. The Receiver operating curve (ROC ) was then plotted from this curve, and the AUC was estimated from the ROC curve.
Measured: Baseline
Radiologist Preference (Arbitrary Units)
To compare radiologist preference of acoustic angiography (AA) to conventional b-mode ultrasound, for each lesion characteristics which are shape, margins, and vascularity, were examined. Radiologists rated their preferences on a Likert scale from 1 to 5, with 1 strongly preferring conventional ultrasound and 5 strongly preferring AA.
Shape, margin, and vascularity values appear to represent mean or median rather than counts. We should select either the mean or the median and provide the standard deviation, which will be 0 if all radiologists assign the same score.
Measured: Baseline
Sensitivity of Acoustic Angiography Compared to Conventional Ultrasound: Breast (Arbitrary Units)
Sensitivity of Acoustic Angiography relative to conventional ultrasound in the analysis of known breast lesions will be evaluated by comparing image analyses to the pathological results for these lesions for both modalities. Sensitivity was calculated based on the formula, which is true positive / (true positive + false negative). The ratio between the sensitivity of AA over the sensitivity of conventional ultrasound was then calculated.
Measured: Baseline
Specificity of Acoustic Angiography Compared to Conventional Ultrasound: Breast (Arbitrary Units)
Specificity of Acoustic Angiography (AA) and conventional ultrasound in the analysis of known breast lesions will be evaluated by comparing image analyses to the pathological results for these lesions for each modality. Specificity was calculated based on the formula, which is true negative / (true negative + false positive). The ratio between the sensitivity of AA over the sensitivity of conventional ultrasound was then calculated.
Measured: Baseline
Sensitivity of Acoustic Angiography Compared to Conventional Ultrasound: Thyroid (Arbitrary Units)
To compare (using a reader study) the sensitivity of acoustic angiography to the sensitivity of conventional b-mode ultrasound in evaluation of known thyroid lesions for predicting malignancy. The study closed early due to insufficient funding and did not reach target enrollment. No participants were enrolled in Arm 2 (Thyroid Imaging); therefore, no outcome measure results are available.
Measured: Baseline
Specificity of Acoustic Angiography Compared to Conventional Ultrasound: Thyroid (Arbitrary Units)
To compare (using a reader study) the specificity of acoustic angiography to the specificity of conventional b-mode ultrasound in evaluation of known thyroid lesions for predicting malignancy. The study closed early due to insufficient funding and did not reach target enrollment. No participants were enrolled in Arm 2 (Thyroid Imaging); therefore, no outcome measure results are available.
Measured: Calculated once all imaging is complete [Anticipated 1.5 years]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2019
- Study start26 May 2022
- Primary completion1 Aug 2024
- Study completion1 Aug 2024
Why it stopped: Grant ended
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Acoustic angiography is a new type of contrast enhanced ultrasound imaging which is specifically sensitive to microvascular structure and density.
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Yueh Lee, MD, PhD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04136912
- Sponsor's protocol ID
- LCCC1915
- Other IDs
- R01CA220681
- Status last verified
- Sep 2025
- First submitted
- 21 Oct 2019
- Last updated
- 6 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Deidentified individual data that supports the results
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High Frame Rate 3-D Super Resolution Ultrasound Microvascular Imaging
- ClinicalTrials.gov ID
- NCT04136912
- Acronym / sponsor ID
- LCCC1915
- Conditions
- Breast Cancer, Thyroid Cancer
- Keywords
- Cancer Screening
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Grant ended
- Enrolment
- 27 participants (actual)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 26 May 2022 (actual)
- Primary completion
- 1 Aug 2024 (actual)
- Study completion
- 1 Aug 2024 (actual)
- First posted
- 23 Oct 2019 (actual)
- Results
- Posted 15 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a 3-arm single center study of 45 patients. These cohorts will include 15 breast patients scheduled to undergo a biopsy, and 15 thyroid patients scheduled to undergo fine needle aspiration, biopsy, or thyroidectomy that consent to undergo an acoustic angiography in conjunction with b-mode ultrasound prior to their scheduled biopsy. Prior to imaging clinical patients, the third arm will include 15 healthy volunteers that will be imaged to optimize imaging parameters.
Detailed description
Increasing the sensitivity and specificity of diagnostic imaging in patients at high risk for breast or thyroid cancer could provide substantial clinical benefit by improving diagnosis, preventing over-treatment, and reducing healthcare costs. Acoustic angiography is a new type of contrast enhanced ultrasound imaging which is specifically sensitive to microvascular structure and density. It evaluates tumor micro-vasculature and may provide a powerful prognostic tool for the diagnosis of breast cancer, and eventually for treatment evaluation.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Acoustic angiography is a new type of contrast enhanced ultrasound imaging which is specifically sensitive to microvascular structure and density.
| Arm | Type | Receives |
|---|---|---|
| Breast Imaging Cohort | Experimental | Drug: Definity, Device: Acoustic AngiographyA total of 15 women with known breast lesions that are already scheduled to undergo a clinical biopsy |
| Thyroid Imaging Cohort | Experimental | Drug: Definity, Device: Acoustic AngiographyA total of 15 participants with known thyroid lesions that are already scheduled to undergo a clinical biopsy |
| Healthy Volunteers Cohort | Experimental | Drug: Definity, Device: Acoustic AngiographyA total of 15 participants will be included to optimize imaging parameters. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Able to provide informed consent
- Negative urine pregnancy test in women of child-bearing potential
- Women
- Patient had a diagnostic breast ultrasound study performed at UNC
- Scheduled for a core needle or surgical breast biopsy of at least one breast lesion that is 2 cm or less in size and 3 cm in depth from the skin surface
Key exclusion criteria (39 listed)
- Institutionalized subject (prisoner or nursing home patient)
- Critically ill or medically unstable and whose critical course during the observation period would be unpredictable (e.g., chronic obstructive pulmonary disease (COPD)
- Known hypersensitivity to perflutren lipid (Definity®)
- Active cardiac disease including any of the following:
- Breast Imaging Patients
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DefinityAlso: perflutrenPerflutren will be administered in split doses using the dosing range and administration type IV bolus) within the perflutren prescribing information. When administered as a bolus, the package insert recommends 10 uL/kg patient weight administered within 30-60 seconds, followed by a 10mL saline flush with a second dose of 10 uL/kg patient weight 30 minutes following the first dose, if needed. | Drug | Breast Imaging Cohort, Healthy Volunteers Cohort, Thyroid Imaging Cohort |
| Acoustic AngiographyAcoustic angiography imaging involves a research ultrasound scanner as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. Imaging will be performed within the package insert guidelines for ultrasound system mechanical index (a measurement of output power) when imaging perflutren contrast agent (less than 0.8). Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes. | Device | Breast Imaging Cohort, Healthy Volunteers Cohort, Thyroid Imaging Cohort |
Primary outcome
Sensitivity of Acoustic Angiography; Breast Imaging
Time frame: Baseline
The sensitivity of Acoustic Angiography in the analysis of known breast lesions will be evaluated by comparing image analyses to the pathological results for these lesions. Sensitivity (%) = True Positives (TP)+False Negatives (FN)True Positives (TP)
Specificity of Acoustic Angiography; Breast Imaging (Percent of Negative Scans)
Time frame: Baseline
Specificity of Acoustic Angiography in the analysis of known breast lesions will be evaluated by comparing image analyses to the pathological results for these lesions. Specificity was calculated based on the formula, which is true negative / (true negative + false positive).
Sensitivity of Acoustic Angiography; Thyroid Imaging (Percent of Positive Scans)
Time frame: Baseline
Sensitivity of Acoustic Angiography in the analysis of know thyroid lesions will be evaluated by comparing image analyses to the pathological results for these lesions. The study closed early due to insufficient funding and did not reach target enrollment. No participants were enrolled in Arm 2 (Thyroid Imaging); therefore, no outcome measure results are available.
Specificity of Acoustic Angiography; Thyroid Imaging (Percent of Negative Scans)
Time frame: Baseline
Specificity of Acoustic Angiography in the analysis of known thyroid lesions will be evaluated by comparing image analyses to the pathological results for these lesions. The study closed early due to insufficient funding and did not reach target enrollment. No participants were enrolled in Arm 2 (Thyroid Imaging); therefore, no outcome measure results are available.
6 secondary outcomes
Area Under the Curve of Acoustic Angiography (Arbitrary Units)
Time frame: Baseline
Radiologist Preference (Arbitrary Units)
Time frame: Baseline
Sensitivity of Acoustic Angiography Compared to Conventional Ultrasound: Breast (Arbitrary Units)
Time frame: Baseline
Specificity of Acoustic Angiography Compared to Conventional Ultrasound: Breast (Arbitrary Units)
Time frame: Baseline
Sensitivity of Acoustic Angiography Compared to Conventional Ultrasound: Thyroid (Arbitrary Units)
Time frame: Baseline
Specificity of Acoustic Angiography Compared to Conventional Ultrasound: Thyroid (Arbitrary Units)
Time frame: Calculated once all imaging is complete [Anticipated 1.5 years]
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Deidentified individual data that supports the results
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yueh Lee, MD, PhD principal investigator
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Definity and Acoustic Angiography in people with Breast Cancer and Thyroid Cancer, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sensitivity of Acoustic Angiography; Breast Imaging (time frame: Baseline). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2025; AzTrials last refreshed its copy on 2 Nov 2026.