Advanced recurrent or metastatic HR+/HER2- breast cancer
Conditions
Interventions
Group 1:Intravenous drip of BEBT-908 and oral administration of Lactuzole Tablets
Group 2:Intravenous drip of BEBT-908 and intramuscular injection of Fulvestrant
Group 3:Intravenous drip of BEBT-908 and intramuscular injection of Fulvestrant
Group 4:Oral administration of BEBT-209, intravenous infusion of BEBT-908, and oral administration of Lactuzole Tablets
Group 5:Oral BEBT-209, intravenous BEBT-908, and intramuscular fulvestrant
Sponsors
Hu'nan Cancer Hospital
Eligibility
Sex/Gender
Female
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Aged >=18 years, female. 2. The patients are willing to sign the informed consent form (ICF) after a comprehensive understanding. 3. Patients with advanced recurrent or metastatic breast cancer diagnosed by histology, immunohistochemical detection of HR positive staining cells >= 10% and HER2 negative (receive the latest metastatic tissue sample or previous primary tumor tissue sample test results), menopausal state or receiving LHRH agonist treatment, there is evidence of focal recurrence or metastasis, not suitable for surgical resection or radiation therapy for the purpose of cure; those who meet any of the following can be considered to have reached the menopausal state: (1) Premenopausal/perimenopausal female patients agree to use concomitant luteinizing hormone-releasing hormone (LHRH agonist), and start receiving LHRH agonist treatment at least 28±2 days before the first dose of study dosing can be considered to meet the inclusion criteria3 (Those who have used LHRH agonist for >=21 days but = 60 years; aged = 12 months, follicle-stimulating hormone (FSH) and estradiol (E2) levels in the postmenopausal range without chemotherapy, tamoxifen, toremifene, or ovarian castration within the past year (judged based on the reference range of each research center); (3) For patients aged = 1500/mm^3 (1.5 x 10^9/L); (2) Platelets >= 100000/mm^3 (100 x 10^9/L); (3) Hemoglobin >= 9g/dL (90g/L); (4) Both ALT or AST are =60mL/min (according to Cockcroft and Gault formula); Note: No blood components, hematopoietic-stimulating factors (including granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, erythropoietin, and thrombopoietin, etc.) are allowed within the first 14 days of screening laboratory tests. 10. All acute toxicities from prior anticancer therapy or surgery resolved to baseline severity or NCI CTCAE version
Exclusion criteria
Exclusion criteria: 1. Advanced patients (patients with visceral crisis) who have symptoms, have spread to the internal organs, and are at risk of developing life-threatening complications in the short term (patients with visceral crisis), inflammatory breast cancer. 2. Combined with any other malignancy (except for adequately treated basal cell or squamous cell skin cancer or cervical carcinoma in situ). 3. Known or symptomatic active CNS metastases manifested by clinical symptoms, cerebral edema, spinal cord compression, cancerous meningitis, leptomeningeal disease, and/or progressive growth. 4. Those who have undergone major surgery within 28 days before the first administration. 5. Received radiotherapy within 28 days before the first dose or required radiotherapy during the trial until 30 days after the last dose; palliative treatment of non-target lesions is not included. 6. Within the specified time frame, before the first dose of the trial drug, received any of the following anticancer treatments: (1) Received any Chinese herbal medicine or Chinese patent medicine with anti-tumor activity within 14 days before the first administration; (2) Received chemotherapy or any investigational drug or other anti-tumor treatment within 21 days before the first dose. 7. The patient has received the following treatments within 7 days before entering the study: (1) Drugs known to be potent inhibitors/inducers of CYP3A4; (2) Drugs known to significantly prolong the QT interval or torsades ventricular tachycardia (antiarrhythmic drugs such as quinidine, disopyramide, procainamide, sotalol, etc.). 8. Those who have received any continuous or intermittent treatment such as PI3K inhibitor, mTOR inhibitor, HDAC inhibitor (does not exclude HDAC inhibitor Chidamide treatment intolerance) before enrollment. 9. Known history of hypersensitivity or suspected hypersensitivity symptoms to any component of BEBT-908, BEBT-209, letrozole/fulvestrant. 10. In the resting state, the average corrected QT interval (QTc) obtained from 3 electrocardiogram (ECG) examinations > 480msec (Only when the first ECG prompts QTc >480msec, it is necessary to retest and take the average correction value of 3 times); history of long QT syndrome or confirmed family history of long QT syndrome; a clinically significant history of ventricular arrhythmias, or current use of antiarrhythmic drugs or implanted defibrillation devices for the treatment of ventricular arrhythmias. 11. Uncontrolled electrolyte disturbances that may affect the effect of QTc-prolonging drugs (such as hypocalcemia = grade 2, atrial fibrillation of any grade, coronary/peripheral artery bypass, symptomatic congestive heart failure, cerebrovascular accident (including transient ischemic attack or symptomatic pulmonary embolism). 13. Grade 2 phlebitis or vasculitis above grade 2 occurs at the site of routine clinical establishment of venous access. 14. Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome or any upper gastrointestinal surgery including gastrectomy; known malabsorption syndrome or other conditions that may impair the absorption of BEBT-209, letrozole. 15. Clinically significant following active infections, including hepatitis B
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate;Pharmacokinetics;Safety and tolerance;Recommended doses for phase II studies;Disease control rate;Onset time;Duration of remission;Progression-free survival;Overall survival; | — |
Countries
China
Contacts
Public ContactQian Changgeng
Outcome results
None listed