HR-positive, HER2-negative locally advanced or metastatic breast cancer
Conditions
Interventions
Combination group:Oral BEBT-209 and intramuscular fluvastatin
Combination Control:Oral placebo and intramuscular fluvastatin
Sponsors
Cancer Hospital Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
Female
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Postmenopausal or premenopausal/perimenopausal female patients over 18 years old, and meet one of the following conditions: previous oophorectomy, or age = 60 years old; or age < 60 years old, natural postmenopausal state (defined as at least 12 consecutive months of spontaneous cessation of regular menstruation without other pathological or physiological reasons), E2 and FSH in the menopausal level, or premenopausal or perimenopausal female patients can also be enrolled, but must be willing to receive luteinizing hormone-releasing hormone (LHRH) agonist therapy during the study; 2. Histologically confirmed HR-positive, HER2-negative breast cancer patients (receiving the test results of tissue samples from recurrent/metastatic lesions or tissue samples from previous primary lesions, based on the latest test results): a) ER-positive and/or PR-positive defined as: ER/PR-positive staining of tumor cells in = 10% of all tumor cells; b) HER2-negative defined as: standard immunohistochemistry (IHC) test results of 0 or 1+; FISH HER2/CEP17 ratio less than 2.0 or HER2 gene copy number less than 4; 3. There is evidence of local recurrence or metastasis, which is not suitable for surgical resection or radiotherapy with the purpose of cure, and there is no clinical necessity for chemotherapy; 4. previous endocrine therapy must meet one of the following conditions: a) progression during or within 12 months after discontinuation of adjuvant endocrine therapy (AI or TAM); b) progression during or within 1 month after discontinuation of the first relapse/metastasis endocrine therapy; 5. No more than 1 line of chemotherapy is allowed for patients with recurrence or metastasis; 6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1; 7. measurable lesions or bone only lesions (including lytic lesions or mixed lesions) meeting RECIST 1.1 criteria; 8. Adequate organ and bone marrow function, defined as follows: absolute neutrophil count (ANC) = 1.5×10^9/L (14 without growth factors); platelets = 100×10^9/L (7 without corrective treatment); hemoglobin = 90g/L (7 without corrective treatment); serum creatinine = 1.5 times the upper limit of normal (ULN); or estimated creatinine clearance = 60mL/min; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 times the upper limit of normal (ULN), patients with liver metastases should be = 5 times the ULN; serum total bilirubin (TBIL) = 2.5 times the ULN; 12 Electrocardiogram: Fridericia's method corrected QT interval (QTcF) < 470 msec (female); 9. Women of childbearing age must have a negative serum pregnancy test within 7 days before the first dose, and are willing to use a medically recognized highly effective contraceptive measure after signing the informed consent form, during the study and within 1 year after the administration of the study drug; 10. all acute toxic reactions from previous anti-tumor therapy resolved to grade 0-1 (according to NCI CTCAE version 5.0) or to the levels specified in the inclusion/exclusion criteria. Alopecia and other toxicities that the investigator considers not to pose a safety risk to the patients; 11. With my consent and signed informed consent, willing and able to comply with scheduled visits, study treatment plan, laboratory tests and other trial procedures.
Exclusion criteria
Exclusion criteria: 1. previous pathological examination diagnosed as HER2-positive breast cancer; 2. Patients who are not suitable for endocrine therapy as judged by the investigator, including symptomatic patients with advanced disease who have disseminated to viscera and are at risk of life-threatening complications in a short period of time (including patients with exudates [thoracic, pericardial, abdominal] that cannot be controlled by drainage or other methods, pulmonary lymphangitis and more than 50% of liver involvement); 3. Known uncontrolled or symptomatic active central nervous system (CNS) metastasis, manifested as clinical symptoms of cerebral edema, spinal cord compression, carcinomatous meningitis, leptomeningeal disease and/or progressive growth; patients with a history of CNS metastasis or spinal cord compression can be studied if they are clearly treated and have stable clinical manifestations 4 weeks after discontinuation of anticonvulsants and steroids before the first dose; 4. previous treatment with drugs such as fulvestrant, everolimus, or CDK4/6 inhibitors; 5. From the end of the last treatment to before the first dose: 4 patients who have undergone surgical treatment or radiotherapy before the first dose and have not completely recovered from the treatment; 4 patients who have received chemotherapy, any investigational drug or other anticancer drug treatment within 5 half-lives of the therapeutic drug (4 weeks or 5 half-lives: those with longer time can be enrolled); 6. have been diagnosed with any other malignant tumor within 3 years before randomization, except for curatively treated non-melanoma skin cancer, basal cell or scaly cell skin cancer or cervical carcinoma in situ; 7. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), active hepatitis B (HBsAg positive patients, and hepatitis B virus load (HBV-DNA) > the upper limit of normal in the laboratory of the center; Patients with hepatitis B DNA quantification > upper limit of normal of the clinical laboratory of the site are allowed to receive antiviral drugs before screening. Only when the virus copy is reduced below the upper limit of normal, patients should receive anti-hepatitis B virus treatment continuously during the trial), hepatitis C (hepatitis C virus antibody positive, and HCV RNA > upper limit of normal of the clinical laboratory of the site) or combined hepatitis B and C co-infection; 8. Within 6 months before randomization, the following conditions: myocardial infarction, severe/unstable angina, NYHA grade 2 or higher cardiac insufficiency, = grade 2 persistent arrhythmia (according to NCI CTCAE version 5.0), any grade of atrial fibrillation, coronary/peripheral artery bypass grafting, symptomatic congestive heart failure, cerebrovascular accident (including transient ischemic attack) or symptomatic pulmonary embolism; 9. 4 weeks Complicated with severe infection (such as intravenous drip of antibiotics, antifungal or antiviral drugs according to clinical diagnosis and treatment specifications) before the first dose, or unexplained fever > 38.5? during screening/before the first dose; 10. inability to swallow, intestinal obstruction or other factors affecting drug administration and absorption; 11. known anticoagulant dysfunction; or the use of anticoagulant therapy before intramuscular injection of fulvestrant or LHRH agonist (Goserelin); 12. known to be allergic to fulvestrant, LHRH agonist (Goserelin),
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free Survival; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective Response Rate;Disease Control Rate;Clinical Benefit Rate;Duration of Response;Overall Survival;Adverse event/Severe adverse event; | — |
Countries
China
Contacts
Public ContactQian Changgeng
BeBetter Med Inc.
Outcome results
None listed