This phase II trial studies how well carboplatin and paclitaxel with or without atezolizumab before surgery works in treating patients with newly diagnosed, stage II-III triple negative breast cancer. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin and paclitaxel, 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. Giving carboplatin and paclitaxel with or without atezolizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PRIMARY OBJECTIVES: I. To test the hypothesis that the combination of chemotherapy and atezolizumab will increase tumor infiltrating lymphocyte (TIL) percentage compared to chemotherapy alone in patients with newly diagnosed triple negative breast cancer (TNBC) being treated with neoadjuvant chemotherapy. II. To test the hypothesis that the combination of chemotherapy and atezolizumab will increase the pathologic complete response (pCR) rate compared to chemotherapy alone in patients with newly diagnosed TNBC being treated with neoadjuvant chemotherapy. SECONDARY OBJECTIVE: I. To evaluate the safety of the treatment combination of atezolizumab + carboplatin + paclitaxel. EXPLORATORY OBJECTIVES: I. To evaluate potential biomarkers of response to chemotherapy in combination with atezolizumab in patients with newly diagnosed TNBC. II. To evaluate the impact of chemotherapy in combination with atezolizumab on the immune response in patients with newly diagnosed TNBC. III. To evaluate the impact of chemotherapy in combination with atezolizumab on neoantigen-specific T cell responses in patients with newly diagnosed TNBC. IV. To evaluate the impact of chemotherapy in combination with atezolizumab on long-term clinical endpoints such as overall survival (OS) and disease-free survival (DFS) in patients with newly diagnosed TNBC. OUTLINE: Patients are randomized into 1 of 2 arms. ARM A: Patients receive carboplatin intravenously (IV) over 30 minutes once every 3 weeks (Q3W) and paclitaxel IV over 1 hour once weekly (QW). Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive atezolizumab IV over 30-60 minutes and carboplatin IV over 30 minutes Q3W, and paclitaxel IV over 1 hour QW. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. In both arms, within 3-6 weeks, patients undergo mastectomy or lumpectomy. Patients also undergo the collection of blood samples throughout the trial. After completion of study treatment, patients are followed up at 6 months and 1 year.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
67
Given IV
Undergo collection of blood samples
Given IV
Undergo lumpectomy
Undergo mastectomy
Given IV
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
Mayo Clinic in Florida
Jacksonville, Florida, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Siteman Cancer Center-South County
St Louis, Missouri, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, United States
...and 4 more locations
Change in Tumor Infiltrating Lymphocyte (TIL) Percentage
Will be measured by histopathologic assay. The TIL percentage after initiation of therapy will be compared between patients receiving neoadjuvant chemotherapy alone (Arm A), and patients receiving neoadjuvant chemotherapy in combination with atezolizumab (Arm B). The post-treatment TIL percentages between two arms will be summarized using descriptive statistics at each time point.
Time frame: Baseline and between days 18-22 following completion of cycle 1 (each cycle is 3 weeks)
Pathologic Complete Response (pCR) Rate
* Pathologic complete response rates will be summarized using contingency tables and compared using Fisher's exact test between patients receiving neoadjuvant chemotherapy alone (Arm A), and patients receiving neoadjuvant chemotherapy in combination with atezolizumab (Arm B). * A pathologic complete response (pCR) is defined as no histology evidence of invasive tumor cells in the surgical breast specimen and sentinel or axillary lymph nodes.
Time frame: At the time of surgery (3-6 weeks after last dose of neoadjuvant chemotherapy, neoadjuvant chemotherapy will be up to 12 weeks in length)
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant
Adverse events were classified and graded using CTCAE version 5.
Time frame: From start of treatment of through completion of AE follow-up (median length of follow-up 2.98 months, full range 0.26-6.56 months)
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