Tucidinostat and Fulvestrant in Hormone-receptor Positive Advanced Breast Cancer

The purpose of the study is evaluate the efficacy and safety of tucidinostat in combination with fulvestrant in patients with hormone-receptor positive advanced breast cancer.

Hormone-receptor positive breast cancer is the most common subtype in breast cancer. Tucidinostat is an oral subtype-selective histone deacetylase inhibitor, which showed preliminary signs of encouraging anti-tumour activity in patients with advanced hormone-receptor positive breast cancer in the previous studies. The aim of this study is to evaluate the efficacy and safety of Tucidinostat in combination with fulvestrant in patients with recurrent or metastatic hormone-receptor positive breast cancer.

Eligibility Criteria:
Inclusion Criteria:

1. Female patients aged 18-75 years (including cutoff value);
2. The disease condition is inoperable, recurrent breast cancer, or metastatic breast cancer;
3. Histological or cytological confirmation of hormone receptor-positive \[estrogen receptor (ER) positive and progesterone receptors (PgR) positive or negative\] breast cancer;
4. At least one measurable lesion according to RECIST 1.1;
5. Prior treatment: have not received systemic chemotherapy for recurrent or metastatic breast cancer;
6. Eastern Cooperative Oncology Group Performance Status of 0-1;
7. Adequate function of major organs meets the following requirements):

   Absolute Neutrophils count≥ 1.5×10\^9/L; Platelets count≥ 90×10\^9/L; Hemoglobin ≥ 90g/L; Total bilirubin≤ 1.5 × the upper limit of normal (ULN); ALT and AST ≤ 2.5 × ULN; BUN and Cr ≤ 1.5 × ULN; Left ventricular ejection fraction (LVEF) ≥ 50%; QTcF(Fridericia correction) ≤ 470 ms; International normalized ratio(INR)≤1.5 × ULN; activated partial thromboplastin time(APTT) ≤ 1.5 × ULN;
8. Life expectancy ≥ 3 months;
9. Have signed informed consent.

Exclusion Criteria:

1. Patients have untreated central nervous system (CNS) metastases;
2. Patients with no measurable lesion according to RECIST 1.1;
3. Patients with bilateral breast cancer;
4. Patients with human epidermal growth factor receptor-2 (Her-2) positive;
5. Recurrent or metastatic disease occurs within 2 years during adjuvant endocrine therapy;
6. Patients previously received systemic chemotherapy for recurrent or metastatic breast cancer;
7. Patients previously received any HDAC inhibitor or fulvestrant treatment;
8. There are ascites, pleural effusion, pericardial effusion with clinical symptoms at baseline, those who need drainage, or those who have undergone drainage of serous effusion within 4 weeks before the first dose;
9. Inability to swallow, intestinal obstruction or other factors affecting the administration and absorption of the drug;
10. Patients with other invasive malignancies within 5 years or at the same time, with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ;
11. Patients with a history of allergies to the drug components of this regimen;
12. Patients with active HBV and HCV infection; stable hepatitis B after drug treatment (HBV virus copy number is higher than the upper limit of reference value) and cured hepatitis C patients (HCV virus copy number exceeds the lower limit of detection method) can be included;
13. Patients with a history of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency disease, history of organ transplantation;
14. Patients have uncontrolled or significant cardiovascular disease, including: Myocardial infarction (\< the last 12 months); Uncontrolled angina (\< the last 6 months); Congestive heart failure (\< the last 6 months), or Left Ventricular Ejection Fraction (LVEF) \< 50% prior to study entry;
15. Any mental or cognitive disorder, that would interfere the ability to understand the informed consent document or the operation and compliance of study;
16. Any other condition which is inappropriate for the study in the opinion of the investigators.