HR-positive, HER2-negative locally advanced or metastatic breast cancer
Conditions
Interventions
Experimental group:Oral administration of BEBT-209 and intramuscular injection of fulvestrant
Control group:Oral placebo and intramuscular fulvestrant
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 bilateral oophorectomy, or age >= 60 years old; or age = 10% of all tumor cells; (2) HER2 negative is defined as: standard immunohistochemistry (IHC) test results are 0 or 1+; FISH test HER2/CEP17 ratio is less than 2.0 or HER2 gene copy number is less than 4; 3. There is evidence of focal recurrence or metastasis, not suitable for curative surgical resection or radiotherapy, and there is no clinical indication for chemotherapy; 4. Previous endocrine therapy must meet one of the following conditions: (1) Progression during or within 12 months after adjuvant endocrine therapy (AI or TAM); (2) Progression during or within 1 month after endocrine therapy for first relapse/transfer; 5. No more than 1 line of chemotherapy is allowed for patients with recurrence or metastasis; 6. Eastern Cooperative Oncology Group (ECOG) physical status score is 0-1; 7. Measurable lesions or only bone metastatic lesions (including osteolytic lesions or mixed lesions) meeting RECIST1.1 criteria; 8. Adequate organ and bone marrow function, defined as follows: absolute neutrophil count (ANC) >= 1.5 x 10^9/L (no growth factor used within 14 days); platelets >= 100 x 10^9/L (7 No corrective treatment within 1 day); hemoglobin >= 90 g/L (no corrective treatment within 7 days); serum creatinine = 1.5 times the upper limit of normal (ULN); or estimated creatinine clearance = 60 mL/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 ULN; serum total bilirubin (TBIL) <= 2.5 times ULN; 12-lead ECG: QT interval corrected by Fridericia method (QTcF) < 470 msec (female); 9. Women of childbearing age must have a serum pregnancy test within 7 days before the first drug administration, and the result is negative, and they are willing to use a medically approved high-efficiency contraceptive measure after signing the informed consent form, during the study period, and within 1 year after the last administration of the study drug ; 10. All acute toxic reactions of previous anti-tumor therapy have been relieved to grade 0-1 (according to NCICTCAE version 5.0) or to the level specified in the inclusion/exclusion criteria. Except for hair loss and other toxicities that researchers believe do not pose safety risks to patients; 11. With my consent and signed informed consent, I am willing and able to follow the planned visits, research treatment plans, laboratory tests and other experimental procedures.
Exclusion criteria
Exclusion criteria: 1. Previous pathological examinations diagnosed as HER2-positive breast cancer; 2. Patients who have been determined by the investigators to be ineligible for endocrine therapy include patients with symptoms, advanced disease that has spread to the viscera, and a short-term risk of life-threatening complications (including patients with exudate (chest, pericardium, abdominal cavity) that cannot be controlled by drainage or other means, pulmonary lymphangitis, and more than 50% liver involvement); 3. Known uncontrolled or symptomatic active central nervous system (CNS) metastasis, manifested as clinical symptoms of cerebral edema, spinal cord compression, cancerous meningitis, leptomeningeal disease and/or progressive growth; Patients with a history of systemic metastasis or spinal cord compression can be included in the study if they have clearly received treatment and are clinically stable after stopping anticonvulsants and steroids for 4 weeks before the first dose; 4. Previously received fulvestrant, everolimus or CDK4/6 inhibitor drug therapy; 5. From the end of the last treatment to before the first administration: surgical treatment or radiotherapy within 4 weeks before the first administration and not fully recovered from the treatment; within 4 weeks before the first administration or within 5 half-lives of the therapeutic drug (4 weeks or 5 half-lives: > Longer time can be included) Received chemotherapy, any investigational drug or other anticancer drug treatment; 6. Any other malignant tumors have been diagnosed within 3 years before randomization, except for curatively treated non-melanoma skin cancer, basal cell or squamous 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 viral load (HBV-DNA) > normal laboratory department of the center The upper limit of the upper limit of the value. Patients with hepatitis B DNA quantification > the upper limit of the normal value of the laboratory department of the center are allowed to use antiviral drugs for treatment before screening. Viral treatment), hepatitis C (positive hepatitis C virus antibody, and HCV RNA > upper limit of normal value of laboratory laboratory of the center) or co-infection of hepatitis B and hepatitis C; 8. Within 6 months before randomization, the following conditions occurred: myocardial infarction, severe/unstable angina, cardiac insufficiency above NYHA grade 2, persistent arrhythmia of grade >= 2 (according to NCI CTCAE 5.0 version), any grade of atrial tremor, coronary/peripheral artery bypass grafting, symptomatic congestive heart failure, cerebrovascular accident (including transient ischemic attack), or symptomatic pulmonary embolism; 9. Severe infection occurred within 4 weeks before the first administration (such as: intravenous infusion of antibiotics, antifungal or antiviral drugs is required according to clinical diagnosis and treatment norms), or unexplained fever > 38.5°C occurred during the screening period/before the first administration; 10. Inability to swallow, intestinal obstruction or other factors affecting drug taking and absorption; 11. Known abnormal anticoagulant function; or use anticoagulant therapy before intramuscular injection of fulvestrant or LHRH agonist (goserelin); 12. Those who are known to be allergic to fulvestrant, LHRH agonist (goserelin), BEBT-209/p
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 ContactChanggeng Qian
Guangzhou Bibet Pharmaceutical Co., LTD
Outcome results
None listed