Tucidinostat and Metronomic Capecitabine for Metastatic Triple-negative Breast Cancer:a Multicenter,Open-label, Randomized Controlled, Phase II Clinical Trial

Inclusion Criteria:

1. ≥18 years old, female; 2. Histologically confirmed triple-negative metastatic breastcancer [HER2 negative is defined as immunohistochemistry(IHC) 0 or IHC 1+, and if the scoreof IHC is 2+, fluorescence in situ hybridization technology (FISH) test must be negative,subjects with ER ≤ 10% and PR ≤ 10% and those with no benefit from endocrine therapy in theinvestigator's judgment are allowed to enroll]; 3. Metastatic breast cancer that has failedat first-line taxane therapy; definition of taxane treatment failure: disease progressionduring rescue therapy, or recurrence and metastasis within 12 months after completion ofadjuvant therapy; 4. ECOG score 0-1; 5. According to RECIST1.1 criteria, at least there isone measurable lesion； 6. The main organ and bone marrow function levels meet the followingrequirements:
2. Blood routine: neutrophil (ANC) ≥ 1.5×109/L; platelet count (PLT) ≥ 90× 109/L;hemoglobin (Hb) ≥ 90g/L; It is required that no blood products (including red bloodcells and platelet products, etc.) have been transfused and no growth factors (including colony-stimulating factor, interleukin, and erythropoietin, etc.) have beenused for supportive treatment within 2 weeks before the examination.
3. Liver function: serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN);alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (withliver Requirements for metastatic patients: ALT and AST≤5×ULN);
4. Renal function: serum creatinine (Cr)≤1.5×ULN or creatinine clearance rate>60mL/min;
5. Expected survival time ≥ 3 months; 8. Voluntary participation study, signed writteninformed consent.

Exclusion Criteria:

1. Known hypersensitivity to capecitabine or tucidinostat; patients with previous severe,unexpected reactions to fluoropyrimidines or known hypersensitivity tofluoropyrimidines;
2. Patients with complete deficiency of dihydropyrimidine dehydrogenase (DPD) activity;
3. Received palliative radiotherapy for target lesion within 4 weeks before enrollment;
4. Previously received treatment with histone deacetylase inhibitors，or have previouslyreceived fluoropicidine drugs such as capecitabine and stopped drugs due to progress (if it is used in the adjuvant phase, then the progress of the treatment within 1 yearafter the suspension of the drug was stopped, and the group cannot be admitted to thestudy).
5. Patients with gastrointestinal perforation, fistula, abdominal abscess,gastrointestinal ulcer or active diverticulosis before enrollment;
6. Significant malnutrition (weight loss > 5% in the past 1 month or > 15% in the past 3months, or food intake decreased by 1/2 or more in the past week), or still need torely on intravenous nutritional support during the screening period;
7. Toxicities that did not recover to National Cancer Institute Common Adverse EventTerminology Version 5.0 (NCICTCAEv5.0) grade 0 or 1 toxicity from prior antineoplastictherapy prior to the first dose of study treatment(alopecia, grade 2 fatigue, grade 2anemia, non-clinically critical and asymptomatic laboratory abnormalities can beenrolled);
8. Patients with currently symptomatic brain or meningeal metastasis;
9. Received immunosuppressive drugs within 4 weeks before enrollment, excluding nasalspray, inhalation or other local glucocorticoids or physiological doses systemicglucocorticoids (no more than 10 mg/day of prednisone or other glucocorticoids at anequivalent dose), or use of glucocorticoids for the prevention of contrast mediumallergy;
10. The patient has any active autoimmune disease or has history of immune disorders (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis,hypophysitis, nephritis, hyperthyroidism, hypothyroidism; patients with vitiligo orcomplete remission of asthma in childhood without any intervention in adulthood can beincluded; those with asthma that require medical intervention with bronchodilators arenot included);
11. Patients with active pulmonary tuberculosis who are receiving anti-tuberculosistreatment or have received anti-tuberculosis treatment within 1 year before screening;
12. Complications requiring long-term use of immunosuppressive drugs, or systemic ortopical use of corticosteroids with immunosuppressive doses;
13. Received any anti-infection vaccine (such as influenza vaccine, chickenpox vaccine,etc.) within 4 weeks before enrollment;
14. Received major surgery (craniotomy, thoracotomy or laparotomy) within 4 weeks beforeenrollment or is expected to undergo major surgery during the study treatment period;received exploratory laparoscopic surgery within 2 weeks prior to enrollment;receivedcentral venous catheterization within 7 days prior to enrollment;
15. Concurrent participation in another interventional clinical study, unlessparticipating in an observational (non-interventional) clinical study or in the safetyfollow-up of an interventional study Stage;
16. Known acute or chronic active hepatitis B (HBsAg positive and HBV DNA virus Load ≥ULNor ≥10^3 copies/mL) or acute or chronic active hepatitis C (HCV antibody positive andHCV RNA positive);
17. Severe heart disease or discomfort, including but not limited to the followingdiseases: 1) Diagnosed history of heart failure or systolic dysfunction (LVEF<50%); 2)arrhythmias requiring medical treatment or clinically significant; 3) high-riskuncontrolled arrhythmias, such as atrial tachycardia, resting heart rate > 100 bpm,significant ventricular arrhythmia (such as ventricular tachycardia) or higher-gradeAV block (ie Mobitz II second-degree AV block or third-degree AV block); 4) Anginapectoris; 5 ) Clinically significant valvular heart disease; 6) ECG shows transmuralmyocardial infarction; 7) Any other heart disease judged by the investigator to beinappropriate to participate in this trial, etc.;
18. Inability to swallow, bowel obstruction, or other factors that interfere with drugtaking and absorption;
19. A history of immunodeficiency, including HIV test positive, or other acquired orcongenital immunodeficiency diseases, or a history of organ transplantation;
20. Pregnant, lactating female patients, female patients of childbearing potential with apositive baseline pregnancy test, or patients of childbearing age who are unwilling touse effective contraception throughout the trial and within 6 months after the laststudy drug;
21. Serious concomitant disease or other comorbidities that would interfere with plannedtreatment;
22. Any other conditions deemed inappropriate by the investigator to participate in thisstudy.