Breast CancerPhase 4NCT04625517
Performance of Contrast-Enhanced Spectral Mammography to Assess Neoadjuvant Chemotherapy Response (CEDM)
A Phase 4 study testing Digital Mammography and Low Osmolar Contrast Material, 300-399 Mg/Ml Iodine Concentration, Per Ml in people with Breast Cancer, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
This study is designed to investigate the diagnostic accuracy of Contrast Enhanced Spectral Mammography (CEDM) in predicting early neoadjuvant therapy response and pathologic complete response (pCR) compared to mammography. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Digital Mammography and Low Osmolar Contrast Material, 300-399 Mg/Ml Iodine Concentration, Per Ml
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jan 2020to 15 Jun 2022
- Phase
- Phase 4
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ipsilateral intact biopsy-proven breast cancer clinical stage T1-T4 (by imaging)
- Available mammography and ultrasound imaging of the existing index cancer, with orthogonal measurements
- Prior history of ipsilateral or contralateral breast cancer, presenting with a new primary or recurrent disease
- Patients who were determined to be candidates for either neoadjuvant chemotherapy or neoadjuvant endocrine therapy by the treating physician
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for days following completion of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Who cannot join
- History of ipsilateral mastectomy
- Women who already started neoadjuvant chemotherapy or endocrine therapy
- Woman who may be pregnant or nursing an infant
- Prior history of anaphylactic or anaphylactoid reaction to any contrast.
- Prior allergy to iodine or iodinated contrast.
- Impaired renal function measured by estimated glomerular filtration rate (eGFR) < 60 milliliters per minute.
- Patients with known distant metastasis.
Trial locations and contacts
1 site in 1 country.
About this study
This study is designed to investigate the diagnostic accuracy of Contrast Enhanced Spectral Mammography (CEDM) in predicting early neoadjuvant therapy response and pathologic complete response (pCR) compared to mammography.
Patients diagnosed with invasive breast cancer with available mammography and ultrasound imaging are eligible for the study.
Eligible patients will be imaged at baseline (before initiation of neoadjuvant chemotherapy or endocrine therapy), early (2-4 cycles of neoadjuvant therapy) and late (after completion of neoadjuvant chemotherapy or endocrine therapy) timepoints with mammography. CEDM will be done within 2 weeks of the specified timepoint. Additionally, a survey of subject experience with CEDM and other pre-operative imaging will be collected after CEDM is performed.
Read the detailed description
The use of neoadjuvant systemic therapy in the treatment of breast cancer patients is increasing beyond the scope of locally advanced disease. Imaging provides important information in assessing response to therapy as a complement to conventional tumor measurements via physical examination. Tumor response to neoadjuvant therapy can also provide prognostic information. The attainment of pCR after completion of neoadjuvant therapy and surgical resection is associated with improved disease-free survival. This correlation is especially strong for Triple-receptor negative and human epidermal growth factor receptor 2 (HER-2) positive breast cancer. Studies of neoadjuvant therapy have used a variety of methods for assessing tumor response. Currently, there are no established clinical practice guidelines for how best to assess tumor response to neoadjuvant therapy. Typically, patients undergo conventional breast imaging such as mammography and ultrasonography (US) and physical examination, and dynamic contrast-enhanced breast magnetic resonance imaging (DCR-MRI) in selected cases.
Contrast Enhanced Digital Mammography (CEDM) is a novel imaging technique, which allows digital mammography to be used with contrast enhancement to depict cancers that would otherwise be occult on standard unenhanced mammography. CEDM is performed with and without intravenous iodine contrast, using the dual energy subtraction technique. Compared with mammography and US, CEDM improves the sensitivity for breast cancer detection without decreasing specificity. CEDM digital detector has higher spatial resolution than MRI, revealing details that are approximately 10 times better. In contrast to the rapid washout in MRI, enhancement on CEDM in fact persists for at least 10 min after contrast agent infusion. Today CEDM is available commercially for clinical use. It is estimated that over 200,000 CEDM examinations have been performed to date in both research and clinical settings. CEDM costs significantly less compared to MRI. Furthermore, longer time delays between contrast injection and CEDM exposure could result in stronger enhancement and hence better visibility compared to MRI, especially given the much higher spatial resolution of digital mammography. It is unknown whether CEDM can improve the sensitivity of mammography in the early assessment of neoadjuvant therapy response. We hypothesize that CEDM is superior to mammography and ultrasound in assessing early response, and pre-surgical residual cancer after neoadjuvant therapy, and when performed, non-inferior to MRI in assessing the residual disease using the metrics of pCR and residual cancer burden (RCB).
- Conditions
- Breast Cancer
- Being tested
- Digital Mammography, Low Osmolar Contrast Material, 300-399 Mg/Ml Iodine Concentration, Per Ml
- Keywords
- mammography, contrast enhanced spectral mammography
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Digital MammographyProcedure or surgery
Digital Mammography enhanced with an iodinated contrast agent
Low Osmolar Contrast Material, 300-399 Mg/Ml Iodine Concentration, Per MlDrug
Injection of low osmolar contrast material during the digital mammography exam
| Study group | Role | What they receive |
|---|---|---|
| Breast cancer patients | Experimental | Patients with ipsilateral intact biopsy-proven breast cancer Receives: Procedure: Digital Mammography; Drug: Low Osmolar Contrast Material, 300-399 Mg/Ml Iodine Concentration, Per Ml |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sensitivity of Predicting pCR (Pathologic Complete Response) for CEDM
Sensitivities in predicting pCR will be calculated for CEDM and measured as AUC
Measured: 4 to 6 months from initiation of neoadjuvant therapy until final surgery
Sensitivity of Predicting pCR (Pathologic Complete Response) for Mammography
Sensitivities in predicting pCR will be calculated for mammography measured as AUC
Measured: 4 to 6 months from initiation of neoadjuvant therapy until final surgery
Specificity of Predicting pCR (Pathologic Complete Response) for CEDM
Specificity of predicting pCR will be calculated for CEDM and measured as AUC
Measured: 4 to 6 months from initiation of neoadjuvant therapy until final surgery
Specificity of Predicting pCR (Pathologic Complete Response) for Mammography
Specificity of predicting pCR will be calculated for mammography and measured as AUC
Measured: 4 to 6 months from initiation of neoadjuvant therapy until final surgery
Diagnostic Accuracy of Contrast-enhanced Mammography in Assessing pCR or Non Response
ROC analysis will be used to assess the diagnostic performance of CEDM. The Area under the receiver operating characteristic (ROC) curve (AUC) will be compared. A leave-one-out cross validation algorithm will be used to reduce bias from overfitting.
Measured: 4 to 6 months from initiation of neoadjuvant therapy until final surgery
Correlation of Residual Tumor Size With Pathologic Size
Spearman's rank correlation will be used to measure the association between final pathologic and imaging tumor size
Measured: 4 to 6 months from initiation of neoadjuvant therapy until final surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2020
- Study start22 Jan 2020
- Primary completion15 Jun 2022
- Study completion15 Jun 2022
Why it stopped: Low enrollment
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 University of Texas Southwestern Medical 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 4
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Basak Dogan, MD, University of Texas Southwestern Medical Center
- Investigators
- Basak Dogan, MD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04625517
- Sponsor's protocol ID
- STU-2019-0529
- Status last verified
- Oct 2023
- First submitted
- 4 Nov 2020
- Last updated
- 12 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Performance of Contrast-Enhanced Spectral Mammography to Assess Neoadjuvant Chemotherapy Response (CEDM)
- ClinicalTrials.gov ID
- NCT04625517
- Acronym / sponsor ID
- STU-2019-0529
- Conditions
- Breast Cancer
- Keywords
- mammography, contrast enhanced spectral mammography
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low enrollment
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- 22 Jan 2020 (actual)
- Primary completion
- 15 Jun 2022 (actual)
- Study completion
- 15 Jun 2022 (actual)
- First posted
- 12 Nov 2020 (actual)
- Results
- Posted 12 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to investigate the diagnostic accuracy of Contrast Enhanced Spectral Mammography (CEDM) in predicting early neoadjuvant therapy response and pathologic complete response (pCR) compared to mammography.
Patients diagnosed with invasive breast cancer with available mammography and ultrasound imaging are eligible for the study.
Eligible patients will be imaged at baseline (before initiation of neoadjuvant chemotherapy or endocrine therapy), early (2-4 cycles of neoadjuvant therapy) and late (after completion of neoadjuvant chemotherapy or endocrine therapy) timepoints with mammography. CEDM will be done within 2 weeks of the specified timepoint. Additionally, a survey of subject experience with CEDM and other pre-operative imaging will be collected after CEDM is performed.
Detailed description
The use of neoadjuvant systemic therapy in the treatment of breast cancer patients is increasing beyond the scope of locally advanced disease. Imaging provides important information in assessing response to therapy as a complement to conventional tumor measurements via physical examination. Tumor response to neoadjuvant therapy can also provide prognostic information. The attainment of pCR after completion of neoadjuvant therapy and surgical resection is associated with improved disease-free survival. This correlation is especially strong for Triple-receptor negative and human epidermal growth factor receptor 2 (HER-2) positive breast cancer. Studies of neoadjuvant therapy have used a variety of methods for assessing tumor response. Currently, there are no established clinical practice guidelines for how best to assess tumor response to neoadjuvant therapy. Typically, patients undergo conventional breast imaging such as mammography and ultrasonography (US) and physical examination, and dynamic contrast-enhanced breast magnetic resonance imaging (DCR-MRI) in selected cases.
Contrast Enhanced Digital Mammography (CEDM) is a novel imaging technique, which allows digital mammography to be used with contrast enhancement to depict cancers that would otherwise be occult on standard unenhanced mammography. CEDM is performed with and without intravenous iodine contrast, using the dual energy subtraction technique. Compared with mammography and US, CEDM improves the sensitivity for breast cancer detection without decreasing specificity. CEDM digital detector has higher spatial resolution than MRI, revealing details that are approximately 10 times better. In contrast to the rapid washout in MRI, enhancement on CEDM in fact persists for at least 10 min after contrast agent infusion. Today CEDM is available commercially for clinical use. It is estimated that over 200,000 CEDM examinations have been performed to date in both research and clinical settings. CEDM costs significantly less compared to MRI. Furthermore, longer time delays between contrast injection and CEDM exposure could result in stronger enhancement and hence better visibility compared to MRI, especially given the much higher spatial resolution of digital mammography. It is unknown whether CEDM can improve the sensitivity of mammography in the early assessment of neoadjuvant therapy response. We hypothesize that CEDM is superior to mammography and ultrasound in assessing early response, and pre-surgical residual cancer after neoadjuvant therapy, and when performed, non-inferior to MRI in assessing the residual disease using the metrics of pCR and residual cancer burden (RCB).
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Breast cancer patients | Experimental | Procedure: Digital Mammography, Drug: Low Osmolar Contrast Material, 300-399 Mg/Ml Iodine Concentration, Per MlPatients with ipsilateral intact biopsy-proven breast cancer |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Ipsilateral intact biopsy-proven breast cancer clinical stage T1-T4 (by imaging)
- Available mammography and ultrasound imaging of the existing index cancer, with orthogonal measurements
- Prior history of ipsilateral or contralateral breast cancer, presenting with a new primary or recurrent disease
- Patients who were determined to be candidates for either neoadjuvant chemotherapy or neoadjuvant endocrine therapy by the treating physician
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for days following completion of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Key exclusion criteria (7 listed)
- History of ipsilateral mastectomy
- Women who already started neoadjuvant chemotherapy or endocrine therapy
- Woman who may be pregnant or nursing an infant
- Prior history of anaphylactic or anaphylactoid reaction to any contrast.
- Prior allergy to iodine or iodinated contrast.
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 |
|---|---|---|
| Digital MammographyDigital Mammography enhanced with an iodinated contrast agent | Procedure or surgery | Breast cancer patients |
| Low Osmolar Contrast Material, 300-399 Mg/Ml Iodine Concentration, Per MlInjection of low osmolar contrast material during the digital mammography exam | Drug | Breast cancer patients |
Primary outcome
Sensitivity of Predicting pCR (Pathologic Complete Response) for CEDM
Time frame: 4 to 6 months from initiation of neoadjuvant therapy until final surgery
Sensitivities in predicting pCR will be calculated for CEDM and measured as AUC
Sensitivity of Predicting pCR (Pathologic Complete Response) for Mammography
Time frame: 4 to 6 months from initiation of neoadjuvant therapy until final surgery
Sensitivities in predicting pCR will be calculated for mammography measured as AUC
Specificity of Predicting pCR (Pathologic Complete Response) for CEDM
Time frame: 4 to 6 months from initiation of neoadjuvant therapy until final surgery
Specificity of predicting pCR will be calculated for CEDM and measured as AUC
Specificity of Predicting pCR (Pathologic Complete Response) for Mammography
Time frame: 4 to 6 months from initiation of neoadjuvant therapy until final surgery
Specificity of predicting pCR will be calculated for mammography and measured as AUC
Diagnostic Accuracy of Contrast-enhanced Mammography in Assessing pCR or Non Response
Time frame: 4 to 6 months from initiation of neoadjuvant therapy until final surgery
ROC analysis will be used to assess the diagnostic performance of CEDM. The Area under the receiver operating characteristic (ROC) curve (AUC) will be compared. A leave-one-out cross validation algorithm will be used to reduce bias from overfitting.
Correlation of Residual Tumor Size With Pathologic Size
Time frame: 4 to 6 months from initiation of neoadjuvant therapy until final surgery
Spearman's rank correlation will be used to measure the association between final pathologic and imaging tumor size
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Breast Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
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.
Basak Dogan, MD principal investigator
University of Texas Southwestern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Digital Mammography and Low Osmolar Contrast Material, 300-399 Mg/Ml Iodine Concentration, Per Ml in people with Breast Cancer, run by University of Texas Southwestern Medical 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 5 inclusion and 7 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 12 Oct 2023. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 12 Oct 2023). 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 Predicting pCR (Pathologic Complete Response) for CEDM (time frame: 4 to 6 months from initiation of neoadjuvant therapy until final surgery). The study lists 6 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 12 Oct 2023.