HER2 and HR positive advanced breast cancer
Conditions
Interventions
Intervention group:Pyrrotinib combined with trastuzumab, Dalcilil and endocrine therapy
Sponsors
Affiliated Cancer Hospital of Harbin Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. The subjects voluntarily joined the study, signed the informed consent, and the compliance was good. 2. Age =18 years old. 3. Patients with locally recurrent or metastatic breast cancer confirmed by histological examination. 4. Premenopausal or perimenopausal patients (if they are such patients, OFS should be combined, and OFS includes both sides Ovariectomy or receiving GnRHa during the study), or postmenopausal patients. 5. Patients with bilateral breast cancer need to confirm that both breast lesions and metastatic lesions are pathological HER2 and HER2 HR positive. 6. HER2 and HR positive invasive breast cancer, following the ASCO/CAP breast cancer HER2 test Guidelines and interpretation criteria for breast cancer ER/PR detection guidelines. HER2 positivity is defined as pathology Laboratory confirmed immunohistochemical (IHC) scores of HER2 3+ or 2+ and in situ hybridization (ISH) test positive, ER positive is defined as immunohistochemical detection of ER expression positive The percentage of tumor cells is =10%. 7. ECOG score 0 to 1. 8. Survival is expected to be not less than 12 weeks. 9. At least one measurable lesion is present according to RECIST 1.1 criteria. 10. Relapsed or advanced stage has not received anti-HER2 therapy, previous adjuvant/neoadjuvant use is allowed Trastuzumab was excessive, but the disease-free interval from the end of the last treatment to tumor progression was required to be =6 months Of the patients. 11. The functional level of the organ must meet the following requirements: 1) Blood routine • ANC=1.5×10 9 /L; • PLT=90×10 9 /L; • Hb=90 g/L; 2) Blood biochemistry • TBIL=1.5×ULN; • ALT and AST=3×ULN (ALT and AST=5×ULN in patients with liver metastasis); • BUN and Cr=1.5×ULN and creatinine clearance =50 mL/min (Cockcroft-Gault formula); 3) Heart color ultrasound • LVEF=50%; 4) 12-lead electrocardiogram Fridericia corrected-Qt Interval (QTcF) for women < 480 ms; 12. Patients with known hormone receptor status
Exclusion criteria
Exclusion criteria: 1. Diffuse liver metastasis, extensive lung cancer lymphangitis, extensive bone marrow metastasis. 2. Inability to swallow, chronic diarrhea and intestinal obstruction, there are multiple factors that affect drug use and absorption. 3. Pial metastasis, brain metastasis or spinal cord compression during active period. Unless the patient is stable (asymptomatic; No evidence of new or emerging brain metastases), and steroid medication should be discontinued before treatment is initiated For at least 14 days, patients with brain metastases, such as radiation and or surgery, must wait after the intervention At 28 days, the disease must be confirmed to be stable by pre-randomization imaging assessment. Screening period detected Asymptomatic CNS, then must wait 28 days after surgery and or radiotherapy intervention, must be mended Imaging before randomization confirmed that the disease was stable. 4. Received radiotherapy, chemotherapy and surgery within 4 weeks before enrollment (excluding local puncture or biopsy) Or molecular targeted immunotherapy. 5. Patients who had received endocrine therapy within 2 weeks before enrollment. 6. Participated in other drug clinical trials within 4 weeks before enrollment. 7. Past adjuvant/neoadjuvant use of aromatase inhibitors (i.e. Anastrozole/letrozole/exemestane) Less than 24 months. 8. Previous use or current use of HER2-targeted tyrosine kinase inhibitors (lapatinib, Lenatinib, pyrrotinib, etc.) or CDK4/6 inhibitors (Piperoxili, Abesili, Da Ersillie et al.). 9. Previous use of fluvestrant. 10. Previous use of HDAC/PAM pathway inhibitors (sidarbenamide, everolimus, etc.). 11. Had other malignant tumors within the past 5 years, excluding cured cervical carcinoma in situ and skin base Cell carcinoma or skin squamous cell carcinoma. 12. Also receive any other anti-tumor therapy. 13. No uncontrolled serous effusion (pleural effusion/peritoneal effusion/pericardial effusion, etc.) within 28 days after intervention Except for those who need to drain again. 14. Known allergic history of the drug components of this protocol; A history of immunodeficiency, including HIV testing Test positive for HCV, syphilis antibody, active viral hepatitis B =ULN or infection Have other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation. 15. Pregnant and lactating women, women with fertility and positive baseline pregnancy test Sex patients. 16. According to the judgment of the researcher, there are serious hazards to the safety of patients or affect the completion of the study Concomitant diseases (including but not limited to severe hypertension that cannot be controlled by medication, severe diabetes) Disease, active infection, etc.). 17. Poorly controlled hypertension (systolic blood pressure =150mmHg or diastolic blood pressure =100mmHg) 18. History of severe heart disease, such as symptomatic congestive heart failure CHF, New York Cardiology NYHA cardiac function rating =2, myocardial infarction or myocardial infarction within 6 months prior to the screening period History of unstable angina. Medically treatable or clinically significant arrhythmia; ren Any other heart conditions that were judged by the investigators to be unsuitable for participation in the study. 19. Have a clear history of neurological or mental disorders, including epilepsy or dementia. 20
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ORR; | — |
Secondary
| Measure | Time frame |
|---|---|
| DCR;CBR;PFS;OS;AE;SAE; | — |
Countries
China
Contacts
Public ContactWenhui Zhao
Affiliated Cancer Hospital of Harbin Medical University
Outcome results
None listed