tucidinostat combined with metronomic capecitabine and endocrine therapy for advanced hr-positive, her2-negative breast cancer after cdk4/6 inhibitor.

Conditions: Breast Cancer

Summary: the study is designed to explore the clinical benefit following treatment with tucidinosta in combination with metronomic capecitabine and endocrine therapy in patients with hormone receptor-positive, her2-negative advanced breast cancer who have received cdk4/6 inhibitor treatment.


Eligibility criteria:
inclusion criteria: 1. ≥18 years old, and ≤75 years old, female; 2. histologically confirmed hr positive and her2 negative postmenopausal metastatic breast cancer patients \[her2 negative is defined as immunohistochemistry(ihc) 0 or ihc 1+, and if the score of ihc is 2+, fluorescence in situ hybridization technology (fish) test must be negative, hr positve is defined as er or pr ≥1%;\]; 3. after the failure of previous cdk4/6 inhibitor therapy; 4.receive one line of chemotherapy at most; 5.premenopausal women need to take effective measures to suppress ovarian function, such as drug suppression, oophorectomy; 6.ecog score 0-1; 7. according to recist1.1 criteria, at least there is one measurable lesion or simple bone metastasis; 8. the main organ and bone marrow function levels meet the following requirements: 1. 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 blood cells and platelet products, etc.) have been transfused and no growth factors (including colony-stimulating factor, interleukin, and erythropoietin, etc.) have been used for supportive treatment within 2 weeks before the examination. 2. liver function: serum total bilirubin (tbil) ≤ 1.5 × upper limit of normal (uln); alanine aminotransferase (alt) and aspartate aminotransferase (ast) ≤ 2.5 × uln (with liver requirements for metastatic patients: alt and ast≤5×uln); 3. renal function: serum creatinine (cr)≤1.5×uln or creatinine clearance rate\>60ml/min; 9. expected survival time ≥ 3 months; 10. voluntary participation study, signed written informed consent. exclusion criteria: 1. known hypersensitivity to any formulation component of the study drug; 2. patients with previous severe, unexpected reactions to fluoropyrimidines or known hypersensitivity to fluoropyrimidines; 3. patients with complete deficiency of dihydropyrimidine dehydrogenase (dpd) activity; 4. visceral crisis; 5. previously received treatment with histone deacetylase inhibitors or fluoropyrimidine drugs such as capecitabine; 6. received chemotherapy, targeted therapy, chinese herbal medicine with anti-tumor indications, or immunomodulatory drugs (including thymosin, interferon, interleukin, etc.) within 4 weeks before enrollment, or still within 5 half-lives of such drugs; 7. received palliative radiotherapy for local lesions within 4 weeks before enrollment; 8. patients with gastrointestinal perforation, fistula, abdominal abscess, gastrointestinal ulcer or active diverticulosis before enrollment; 9. significant malnutrition (weight loss \> 5% in the past 1 month or \> 15% in the past 3 months, or food intake decreased by 1/2 or more in the past week), or still need to rely on intravenous nutritional support during the screening period; 10. toxicities that did not recover to national cancer institute common adverse event terminology version 5.0 (ncictcaev5.0) grade 0 or 1 toxicity from prior antineoplastic therapy prior to the first dose of study treatment(alopecia, grade 2 fatigue, grade 2 anemia, non-clinically critical and asymptomatic laboratory abnormalities can be enrolled); 11. patients with currently symptomatic brain or meningeal metastasis; 12. received immunosuppressive drugs within 4 weeks before enrollment, excluding nasal spray, inhalation or other local glucocorticoids or physiological doses systemic glucocorticoids (no more than 10 mg/day of prednisone or other glucocorticoids at an equivalent dose), or use of glucocorticoids for the prevention of contrast medium allergy; 13. 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 or complete remission of asthma in childhood without any intervention in adulthood can be included; those with asthma that require medical intervention with bronchodilators are not included); 14. patients with active pulmonary tuberculosis who are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before screening; 15. complications requiring long-term use of immunosuppressive drugs, or systemic or topical use of corticosteroids with immunosuppressive doses; 16. received any anti-infection vaccine (such as influenza vaccine, chickenpox vaccine, etc.) within 4 weeks before enrollment; 17. received major surgery (craniotomy, thoracotomy or laparotomy) within 4 weeks before enrollment or is expected to undergo major surgery during the study treatment period; received exploratory laparoscopic surgery within 2 weeks prior to enrollment;received central venous catheterization within 7 days prior to enrollment; 18. concurrent participation in another interventional clinical study, unless participating in an observational (non-interventional) clinical study or in the safety follow-up of an interventional study stage; 19. known acute or chronic active hepatitis b (hbsag positive and hbv dna virus load ≥uln or ≥10\^3 copies/ml) or acute or chronic active hepatitis c (hcv antibody positive and hcv rna positive); 20. severe heart disease or discomfort, including but not limited to the following diseases: 1) diagnosed history of heart failure or systolic dysfunction (lvef\ 100 bpm, significant ventricular arrhythmia (such as ventricular tachycardia) or higher-grade av block (ie mobitz ii second-degree av block or third-degree av block); 4) angina pectoris; 5 ) clinically significant valvular heart disease; 6) ecg shows transmural myocardial infarction; 7) any other heart disease judged by the investigator to be inappropriate to participate in this trial, etc.; 21. inability to swallow, bowel obstruction, or other factors that interfere with drug taking and absorption; 22. a history of immunodeficiency, including hiv test positive, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; 23. pregnant, lactating female patients, female patients of childbearing potential with a positive baseline pregnancy test, or patients of childbearing age who are unwilling to use effective contraception throughout the trial and within 6 months after the last study drug; 24. serious concomitant disease or other comorbidities that would interfere with planned treatment; 25. any other conditions deemed inappropriate by the investigator to participate in this study.

Keywords: metronomic capecitabine endocrine therapy histone deacetylase inhibitor metastatic breast cancer