a single-arm, prospective phase ⅱ clinical study of utidelone combined with capecitabine in the treatment of active brain metastasis of tnbc

Conditions: Metastatic Breast Cancer

Summary: this study aims to explore the efficacy and safety of the combination therapy of utidelone and capecitabine in the treatment of brain metastases from triple-negative advanced breast cancer, and to search for systemic treatment for brain metastases from triple-negative advanced breast cancer cases.


Eligibility criteria:
inclusion criteria: 1. age ≥18 years old; 2. invasive breast cancer confirmed by histological or cytological examination, accompanied by metastatic disease; patients with metastatic diseases not confirmed by pathology or cytology should obtain clear evidence of metastasis through physical examination or radiological research; 3. based on the pathological report of recent biopsy or other pathological specimens (confirmed by the laboratory of the participating research center), the histology and/or cytology are confirmed as triple negative breast cancer. the specific requirements include: a) the definition of negative human epidermal growth factor receptor 2(her2): the immunohistochemistry (ihc) is 0 or 1+; if ihc was 2+, it was confirmed negative by fluorescence in situ hybridization (fish). b) negative estrogen and progesterone receptors means that ihc examination shows er \< 10% and or pr \< 10%, and the researcher evaluates that patients cannot benefit from endocrine therapy. 4. newly diagnosed brain metastases or brain metastases that have progressed after local treatment: patients with brain metastases who met all the criteria of this scheme before starting from september 1, 2023 and did not meet all the exclusion criteria can also be included; 5. patients must have measurable central nervous system diseases, defined as at least one brain parenchymal lesion, which can be accurately measured in at least one dimension through local radiological examination; and there is no central nervous system symptom or symptom controllable, so radiotherapy is not needed urgently. 6. patients who have previously received at least one taxane and/or one anthracycline antibiotic (as a treatment history of neoadjuvant therapy, adjuvant therapy or metastatic therapy or both); 7. allow (new) adjuvant therapy to have recurrence and metastasis after stopping using utterone and/or capecitabine for more than one year, or stop taking drugs for non-progressive reasons in the rescue stage; 8. the physical status score (ecogps) of the eastern cancer cooperative group is 0-2, and the life expectancy is more than 12 weeks; 9. normal organ and bone marrow function; blood routine examination was basically normal within one week before joining the group (based on the normal laboratory of each research center): neutrophil count (anc) ≥ 1.5× 109/l; hemoglobin (hb) ≥ 90g/l; platelet count (plt) ≥ 75× 109/l; liver and kidney function tests were basically normal within one week before enrollment (based on the normal values of laboratories in each research center): total bilirubin (tbil)≤1.5× upper limit of normal value (uln); alanine aminotransferase (sgpt/alt)≤2.5×uln (patients with liver metastasis ≤ 5 xuln); aspartate aminotransferase (sgot/ast)≤2.5× upper limit of normal value (uln); creatinine clearance rate (ccr)≥60ml/min. 10. neuropathy should be \< grade 2 within 4 weeks before enrollment (version 5.0 of ncictcae); 11. no major organ dysfunction and no heart disease; 12. women and male patients with reproductive potential must agree to use appropriate contraceptive measures before the start of the study and during the study participation. exclusion criteria: 1. patients with extensive meningeal metastasis and brain metastasis who are ineffective in dehydration treatment with hormones or in urgent need of radiotherapy; 2. invasive breast cancer confirmed by histological or cytological examination, accompanied by metastatic disease; patients with metastatic diseases not confirmed by pathology or cytology should obtain clear evidence of metastasis through physical examination or radiological research; 3. received chemotherapy, major surgery, targeted therapy or immunotherapy within 2 weeks before joining the group (the interval between targeted therapy and immunotherapy is at least 2 weeks or at least 5 half-lives, whichever is shorter); received endocrine therapy within 1 week before joining the group; he had received nitrosourea or mitomycin chemotherapy within 6 weeks before joining the group; 4. receive unlisted clinical trial drugs within 4 weeks before entering the group; 5. previous history of grade 3 or 4 allergic reactions related to utterone or capecitabine; 6. inability to swallow, chronic diarrhea and intestinal obstruction, there are many factors that affect the taking and absorption of drugs; 7. known contraindications for gadolinium mri contrast agents, such as pacemakers, shrapnel or ocular foreign bodies; 8. suffering from other malignant tumors in the past 3 years, excluding cured cervical carcinoma in situ, basal cell carcinoma of skin, squamous cell carcinoma of skin or early thyroid carcinoma; 9. seizures occurred more than 2 times within 4 weeks before joining the group; 10. poor control of hypertension; or have a history of hypertensive crisis or hypertensive encephalopathy; 11. have a history of bleeding in the central nervous system of grade 3 or above within 12 months; 12. suffering from serious or uncontrollable diseases, including but not limited to: 1) active virus infection, such as hiv and hbv active phase (hbsag positive and hbv-dna≥103, hepatitis c antibody positive); 2) suffering from severe cardiovascular disease in the past: uncontrollable hypertension; myocardial infarction, unstable arrhythmia, congestive heart failure, pericarditis, myocarditis, etc. according to nyha criteria, patients with grade ⅲ \~ ⅳ cardiac insufficiency, or those with left ventricular ejection fraction (lvef) less than 50% indicated by echocardiography; 12. suffering from serious or uncontrollable diseases, including but not limited to: 1) active virus infection, such as hiv and hbv active phase (hbsag positive and hbv-dna≥103, hepatitis c antibody positive); 2) suffering from severe cardiovascular disease in the past: uncontrollable hypertension; myocardial infarction, unstable arrhythmia, congestive heart failure, pericarditis, myocarditis, etc. according to nyha criteria, patients with grade ⅲ \~ ⅳ cardiac insufficiency, or those with left ventricular ejection fraction (lvef) less than 50% indicated by echocardiography; 13. have a history of hemoptysis within 6 months before joining the group; or evidence of bleeding tendency or obvious coagulation dysfunction in the last month; 14. currently receiving full-dose warfarin or equivalent drugs, or taking aspirin (325mg/ day) within 10 days; 15.28 days or in the course of the study, it is expected that major surgery, open biopsy or major trauma are needed; 16. those who have a history of abdominal fistula or gastrointestinal perforation in the first 6 months; there are unhealed wounds, active ulcers or untreated fractures; pregnant or lactating women; 17. those who have a history of psychotropic substance abuse and cannot quit or patients with mental disorders; 18. according to the judgment of the researcher, there are other patients with accompanying diseases that seriously endanger the safety of patients or affect the completion of the study; 19. those who are known to have allergic history to the drug components of this scheme; have a history of immunodeficiency, including hiv positive, hcv or other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation; 20. the history of live attenuated vaccine inoculation within 28 days before the first study or the person who is expected to be vaccinated with live attenuated vaccine in the study; 21. any situation that the researcher thinks is not suitable for this study.