Testing the Addition of an Anti-cancer Drug, ASTX727 (Cedazuridine, Decitabine), to Chemotherapy (Paclitaxel) and Immunotherapy (Pembrolizumab) for Metastatic Triple-Negative Breast Cancer
Trial Parameters
Brief Summary
This phase I trial tests the safety, side effects, and best dose of ASTX727 when given in combination with a usual approach of treatment with paclitaxel and pembrolizumab in patients with triple-negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). The usual approach is defined as care most people get for this type of cancer. The usual approach for patients with metastatic triple negative breast cancer who are not in a study is chemotherapy with drugs like paclitaxel, carboplatin, cisplatin, eribulin, vinorelbine, capecitabine, gemcitabine, doxorubicin or cyclophosphamide. There is a protein called PD-L1 that helps regulate the body's immune system. For patients who have PD-L1+ tumors, immunotherapy (pembrolizumab) is usually added to paclitaxel or carboplatin/gemcitabine as initial treatment. For patients who have PD-L1-negative tumors, chemotherapy alone is used, without immunotherapy. ASTX727 is a combination of two drugs, decitabine and cedazuridine. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving ASTX727 with usual treatment approach with paclitaxel and pembrolizumab may be able to shrink or stabilize the tumor for longer than the usual approach alone in patients with metastatic triple negative breast cancer.
Eligibility Criteria
Inclusion Criteria: * Patients must have histologically confirmed triple-negative breast cancer (TNBC) (estrogen receptor \[ER\] and progesterone receptor \[PR\] =\< 10%, human epidermal growth factor receptor-2 \[HER2\]-negative per American Society of Clinical Oncology \[ASCO\]/College of American Pathologists \[CAP\] guidelines) that is metastatic or unresectable * Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of ASTX727 in combination with pembrolizumab (MK-3475) and paclitaxel in patients \< 18 years of age, children are excluded from this study * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (or Karnofsky \>= 60%) * Absolute neutrophil count (ANC) \>= 1500/mm\^3 (within 14 days prior to registration) * Platelets \>= 100,000/mm\^3 (within 14 days prior to registration) * Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L (within 14 days prior to registration) * Criteria must be met without packed red blood cell (pRBC) transf