An official website of the United States government
Neoadjuvant Response-Adapted Chemotherapy with Pembrolizumab for the Treatment of Patients with Stage 2 and 3 Triple Negative Breast Cancer
Trial Status: active
This phase II trial tests how well changes in imaging and blood and tissue samples work to determine response to treatment when giving response adapted chemotherapy with pembrolizumab for patients with stage 2 or 3 triple negative breast cancer. The current standard of care is to administer the entire 6-month chemotherapy treatment irrespective of clinical response. This study tests administering the first 3 months of standard of care therapy, with pembrolizumab, paclitaxel and carboplatin, and then evaluating the response to treatment either proceeding with additional chemotherapy, followed by surgery or proceeding directly with surgery. After surgery patients are evaluated again and receive standard of care pembrolizumab or additional chemotherapy. Chemotherapy drugs, such as pembrolizumab, paclitaxel, and carboplatin work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Receiving response adapted chemotherapy may be effective and require less treatment for patients with stage 2 and 3 triple negative breast cancer.
Inclusion Criteria
Stage II-III TNBC
* estrogen receptor (ER)/progesterone receptor (PR) up to and including 10% is eligible
Age ≥ 18 years
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
Eligible for standard chemo-immunotherapy as determined by treating physician, including consideration of:
* Adequate marrow and organ function
* Co-morbid conditions do not preclude the use of chemo-immunotherapy (such as uncontrolled autoimmune disease, or the use of immunosuppressive medications)
Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study
Exclusion Criteria
Patients unable to undergo PET or MRI
Evidence of metastatic disease or loco-regional recurrence (i.e. distant or chest wall recurrence)
Inflammatory breast cancer
Previous treatment with paclitaxel, carboplatin, or immune checkpoint inhibitors
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT06245889.
I. To evaluate if lack of decrease in fludeoxyglucose (FDG)/positron emission tomography (PET) standardized uptake value normalized to lean body mass (SUL) max by < 40% after 1 cycle of neoadjuvant therapy correlates with residual disease at the time of surgery (negative predictive value [NPV] of PET with residual disease [RD]).
SECONDARY OBJECTIVES:
I. To evaluate the pathologic complete response (pCR) rate in patients with early-stage triple negative breast cancer (TNBC) treated with neoadjuvant chemo-immunotherapy.
II. To evaluate the diagnostic accuracy of percent and absolute change (between baseline and cycle 1 day 15 [C1D15] measurements), and C1D15 absolute measurements in FDG/PET SULmax for predicting pCR using receiver operating characteristic (ROC) curve.
EXPLORATORY OBJECTIVES:
I. To compare the pCR rates among patients who achieved clinical complete response (cCR) by magnetic resonance imaging (MRI) and those received “rescue” neoadjuvant doxorubicin/cyclophosphamide (AC)/pembrolizumab (pembro) with clinical residual disease (RD) after MRI scan.
II. To evaluate the diagnostic accuracy of percent and absolute change (between baseline and C1D15 measurements), and C1D15 absolute measurements in FDG/PET SULmax for predicting cCR using ROC curve.
III. To investigate if cCR by MRI is predictive of pCR.
IV. To evaluate if clearance of circulating tumor deoxyribonucleic acid (ctDNA) correlates with pCR.
V. To characterize genomic, pathologic, and other molecular features of the tumor microenvironment (TME) and other patient factors (ie microbiome) serially over time of residual disease.
OUTLINE:
Patients receive paclitaxel intravenously (IV) and carboplatin IV on days 1, 8 and 15 and pembrolizumab IV on day 1 of each cycle. Cycles repeat every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with a complete response to treatment undergo standard of care surgery. Patients with clinical residual disease undergo additional chemotherapy and may undergo surgery as determined by their treating physician. After surgery patients with a pathologic complete response receive pembrolizumab per standard of care and patients with residual disease may receive additional chemotherapy per their treating physician. Patients undergo PET scan and blood sample collection throughout the study.
After completion of study treatment, patients are followed up yearly for 3 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationJohns Hopkins University/Sidney Kimmel Cancer Center
