Hormone Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer with Recurrence or Progression after CDK4/6 Inhibitor plus Endocrine Therapy
Conditions
Interventions
Experimental group:Entinostat in Combination with Fulvestrant
Sponsors
Sun Yat-sen University Cancer Center
Eligibility
Sex/Gender
Female
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Sign the informed consent form; 2. Female, aged between 18 and 75 years; 3. The Eastern Cooperative Oncology Group (ECOG) performance status of the patient is 0-1; 4. The patient's expected survival time is = 3 months; 5. The patient is diagnosed with HR-positive and HER-2-negative breast cancer based on tumor histopathology and molecular pathology (based on the most recent report); (1) Hormone receptor positive means that the estrogen receptor (ER) is positive (>= 10% stained cells are considered positive), and the progesterone receptor (PR) is negative or positive (>= 10% stained cells are considered receptor positive); (2) HER-2 negative means: the immunohistochemical result of the pathological specimen is 0 or 1+; or the immunohistochemical result is 2+ and the ISH or FISH test is negative. 6. The subject needs to have received CDK4/6 inhibitor combined with endocrine therapy, and meet any of the following conditions, that is, endocrine resistance: (1) There is imaging progression during adjuvant or neoadjuvant endocrine therapy; Or (2) Recurrence or metastasis occurs within = 12 months after completion of adjuvant endocrine therapy; Or (3) Disease progression occurs after the first-line endocrine therapy in the advanced stage (according to RECIST v1.1). 7. The patient's chemotherapy treatment history must meet the following requirements: (1) For metastatic disease, they have received = 4 weeks; (3) If disease progression occurs = 80 g/L, platelet count >= 50 × 10^9 /L, absolute neutrophil count >= 1.0 × 10^9 /L. Note: Before these laboratory tests, platelet transfusion is not allowed within 3 days, red blood cell transfusion is not allowed within 14 days, and hematopoietic growth factor transfusion (PEGylated G-CSF for granulocyte colony-stimulating factor is 14 days) is not allowed within 7 days. Renal function: Serum creatinine (Cre) = 60 mL/min/1.73m2. Liver function: Total bilirubin = 50%, and QTc interval = 60 years; (3) Age = 12 months, without chemotherapy, tamoxifen, toremifene, or ovarian castration, and the levels of blood follicle-stimulating hormone (FSH) and estradiol (E2) are within the postm
Exclusion criteria
Exclusion criteria: 1.Presence of current or prior Central Nervous System (CNS) metastases or leptomeningeal disease (LMD).? 2.?Prior treatment with Selective Estrogen Receptor Degraders (SERD, e.g., fulvestrant) or Histone Deacetylase (HDAC) inhibitors (e.g., entinostat, chidamide).? 3?.Known hypersensitivity to SERDs, entinostat, or other benzamide-structured drugs (e.g., tiapride, remoxipride, clebopride). 4.?Pregnancy or lactation.? 5.?Concurrent malignancies except those curatively treated with no recurrence/metastasis within 5 years. 6.Clinically significant effusions requiring drainage? (e.g., pericardial, pleural, or ascites with symptoms). 7.?Severe gastrointestinal dysfunction impairing drug absorption? (e.g., dysphagia, chronic diarrhea, intestinal obstruction). 8.Within 14 days prior to enrollment?: Uncontrolled severe infections; Uncontrolled cardiovascular disease; ?Any condition deemed by the investigator to compromise safety or compliance.? 9.Patients deemed by investigators as unsuitable for endocrine therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival, PFS; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate, ORR;Duration of Response, DOR;Clinical benefit rate, CBR;Overall survival, OS;Treatment compliance;Health-related quality of life, HRQL; | — |
Countries
China
Contacts
Public ContactWang Shusen
Sun Yat-sen University Cancer Center
Outcome results
None listed