Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Triple-Negative Breast Carcinoma
Conditions
Brief summary
This clinical trial studies how well ultrasound/photoacoustic/elasticity (US/PA/E) imaging works for early identification of tumor response in patients with stage II-III triple-negative breast cancer receiving immunotherapy and chemotherapy before surgery (neoadjuvant). US imaging uses high-energy sound waves to look at tissues and organs inside the body. The sound waves make echoes that form pictures of the tissues and organs on a computer screen. PA imaging delivers laser light into tissue which produces ultrasonic waves which are then converted into images. Elastography (i.e., elasticity \[E\]) imaging uses sound waves to send vibrations into a specific organ and measures how fast those vibrations move. The vibrations move faster through areas of stiff tissue and a computer uses these measurements to make an image of those areas. Combined US/PA/E imaging using the Vevo F2 and Vevo LAZR-X20 devices may be safe and provide earlier information about tumor response to standard neoadjuvant immunotherapy and chemotherapy than current standard imaging.
Detailed description
PRIMARY OBJECTIVE: I. To evaluate the change pattern of the US/PA/E imaging biomarkers (primarily deoxy hemoglobin) over the neoadjuvant treatment course and assess the association with clinical response as assessed by comparing baseline and presurgical magnetic resonance imaging (MRI). SECONDARY OBJECTIVE: I. To assess the ability of the US/PA/E imaging protocol to identify patient response early in the neoadjuvant treatment course of patients with stage II-III triple-negative breast cancer (TNBC) receiving neoadjuvant pembrolizumab and chemotherapy and predict pathologic complete response (pCR). OUTLINE: Patients undergo US imaging using the Vevo F2 device and PA/E imaging using the Vevo LAZR-X20 device prior to and at week 4 and week 7 of standard of care (SOC) carboplatin, pembrolizumab, and paclitaxel regimen, prior to cycles 1 and 2 of SOC doxorubicin, cyclophosphamide, pembrolizumab regimen, as well as prior to SOC surgery. Patients also undergo breast MRI on study.
Interventions
PROCEDUREElastography
Undergo PA/E imaging using the Vevo LAZR-X20 device
PROCEDUREMagnetic Resonance Imaging
Undergo breast MRI
PROCEDUREPhotoacoustic Imaging
Undergo PA/E imaging using the Vevo LAZR-X20 device
PROCEDUREUltrasound Imaging
Undergo US imaging using the Vevo F2 device
DRUGPembrolizumab
Weekly carboplatin + paclitaxel +every three- week pembrolizumab X12 weeks, followed by every three-week doxorubicin + cyclophosphamide (AC) + pembrolizumab X 4 cycles).
DRUGCarboplatin
Weekly carboplatin + paclitaxel +every three- week pembrolizumab X12 weeks, followed by every three-week doxorubicin + cyclophosphamide (AC) + pembrolizumab X 4 cycles).
DRUGPaclitaxel
Weekly carboplatin + paclitaxel +every three- week pembrolizumab X12 weeks, followed by every three-week doxorubicin + cyclophosphamide (AC) + pembrolizumab X 4 cycles).
DRUGDoxorubicin
Weekly carboplatin + paclitaxel +every three- week pembrolizumab X12 weeks, followed by every three-week doxorubicin + cyclophosphamide (AC) + pembrolizumab X 4 cycles).
DRUGCyclophosphamide
Weekly carboplatin + paclitaxel +every three- week pembrolizumab X12 weeks, followed by every three-week doxorubicin + cyclophosphamide (AC) + pembrolizumab X 4 cycles).
Sponsors
Emory University
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Patients with stage II-III triple negative breast cancer, per American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) guidelines * Deemed clinically appropriate for KEYNOTE-522 regimen based on performance status and laboratory findings * No signs of metastatic disease * Female patients must have a negative urine or serum pregnancy at screening (pregnancy test is not required for patients with bilateral oophorectomy and/or hysterectomy or for those patients who are \> 1 year postmenopausal) * All patients of reproductive potential must agree to use an approved form of contraception * Must provide informed consent
Exclusion criteria
* Acute bacterial or fungal infection requiring intravenous (IV) antibiotics at time of registration * Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serial changes in the ultrasound/photoacoustic/elasticity (US/PA/E) imaging biomarkers | Baseline up to time of surgery (24 weeks) | Will evaluate serial changes in the US/PA/E imaging biomarkers (primarily deoxy hemoglobin) over the course of the treatment and their association with clinical response as assessed by comparison of baseline and pre surgical magnetic resonance imaging. Summary statistics and data visualization will be applied to describe the biomarker data at each time point, along with the changing patterns during the treatment period. A paired t-test or Wilcoxon signed rank test will test the magnitude change of optical images at week-3 from baseline. A linear and/or non-linear mixed effect model will be considered to model the longitudinal data and test the trend of change. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between the early changes documented in US/PA/E protocol and the probability of achieving pathologic complete response (pCR) | Up to 24 weeks | Will compare the correlation between the early changes documented in US/PA/E protocol and the probability of achieving pCR, defined as pT0/T1s, pN0. To predict the status of clinical response (Aim 1) or pCR (Aim 2), the value of the biomarker at each timepoint and their change relative to the baseline value (e.g fold-change or percentage of change) will be treated as continuous variables, and receiver operator characteristics analysis will be applied to assess the overall prediction performance in terms of the area under the curve, and to identify the optimal cut-off value and/or the optimal timepoint that results in the best prediction performance in terms of the sensitivity and specificity. |
Countries
United States
Contacts
CONTACTKevin Kalinsky, MD, MS, FASCO
PRINCIPAL_INVESTIGATORKevin Kalinsky, MD, MS, FASCO
Emory University Hospital/Winship Cancer Institute
Outcome results
None listed