| Eligibility |
Inclusion Criteria:
- 1. Patients voluntarily participated in the study and signed informed consent;
- 2. Women aged 18 or older;
- 3. The number of treatment lines shall not exceed 4 lines;
- 4. Patients with locally advanced or metastatic breast cancer diagnosed as
HER2-negative by molecular typing;
- 5. Enrolled patients were HER2-negative breast cancer patients who had failed to prior
taxane and/or anthracycline therapy, or patients with hormone receptor-positive
HER2-negative advanced breast cancer who had progressed with at least prior first-line
endocrine therapy;
- 6. ECOG score is 0 or 1, and the expected survival is not less than 3 months;
- 7. Patients with measurable lesions as defined in RECIST1.1 criteria;
- 8. The main organs function well, and the laboratory test indexes meet the following
requirements:(1) Routine blood test (no blood transfusion or hematopoietic stimulating
factor was used within 7 days before screening) :? Hemoglobin (HB) = 90g/L;? Absolute
neutrophil count (ANC) =1.5×109/L;? Platelet (PLT) = 80×109/L;(2) Blood biochemical
test (no blood transfusion or albumin within 7 days before screening) :? ALT and AST
=2.5 × ULN (liver/bone metastasis =5 × ULN; Bone metastases =5 ULN);? Serum total
bilirubin (TBIL) =1.5 × ULN;? Serum Cr=1.5×ULN or creatinine clearance =60 mL /min;(3)
Coagulation function test:? Activated partial thrombin time (APTT), international
standardized ratio (INR), prothrombin time (PT) = 1.5×ULN;? Doppler ultrasound
assessment: left entricular ejection fraction (LVE F)= 50%;
- 9. The patient has the ability to take medication orally;
- 10. Any toxic side effects of previous chemotherapy have been recovered to =CTCAE1 or
baseline level;
- 11. Women of reproductive age must agree to use a highly effective method of
contraception during the study period and for 6 months after the last administration
of the study drug; Negative serum or urine pregnancy test within 7 days prior to study
enrollment and must be non-lactating subjects;
Exclusion Criteria:
- 1. Prior treatment with bevacizumab, anlotinib and other antiangiogenic agents;
- 2. Patients who had previously used Vinorelbine with an interval time of less than 6
months from the end of medication;
- 3. Interval of less than 3 weeks after radiotherapy or chemotherapy; The interval
after endocrine therapy was less than 1 week;
- 4. Associated diseases/history;(1) Clinically significant hemoptysis occurred within 3
months before enrollment (hemoptysis > 50ml per day); Or bleeding symptoms of
significant clinical significance or a clear bleeding tendency, such as
gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occultation and
above, or suffering from vasculitis, etc.;(2) Arteriovenous thrombosis events occurred
within 6 months before enrollment, such as cerebrovascular accident (including
temporary ischemic attack), deep venous thrombosis (except those who had been cured
after intravenous catheterization due to chemotherapy) and pulmonary embolism,
etc.;(3) hypertension, which cannot be well controlled by antihypertensive drug
therapy (systolic blood pressure & GT; 140 mmHg or diastolic pressure > 90 mmHg);
During the first 6 months of randomization, myocardial infarction, severe/unstable
angina, NYHA grade 2 or higher cardiac dysfunction, clinically significant ventricular
arrhythmias or ventricular arrhythmias, and symptomatic congestive heart failure;(4)
Interstitial lung disease, non-infectious pneumonia or uncontrollable systemic
diseases (e.g., diabetes, pulmonary fibrosis and acute pneumonia);(5) Renal
insufficiency: urine protein = ++ indicated by routine urine examination, or confirmed
24-hour urine protein level =1.0g;(6) History of live attenuated vaccine vaccination
within 28 days prior to initial study administration or expected live attenuated
vaccine vaccination during study period;(7) human immunodeficiency virus (HIV)
infection or known acquired immunodeficiency syndrome (AIDS); Active hepatitis
(hepatitis B, defined as HBV-DNA = 500 IU/ mL; Hepatitis C, defined as hcV-RNA higher
than the lower limit of assay) or co-infection with hepatitis B and c;(8) Severe
infection, including but not limited to bacteremia and severe pneumonia requiring
hospitalization, occurred within 4 weeks before the first administration; Active CTCAE
grade 5.0=2 infection requiring systemic antibiotic treatment within 2 weeks prior to
initial administration or unexplained fever during screening/prior to initial
administration > 38.5°C (according to the investigator's judgment, fever caused by
tumor can be included in the group); Evidence of active tuberculosis infection within
1 year before administration;
- 5. Have been diagnosed with any other malignant tumor within 3 years prior to entering
the study;
- 6. Thyroid dysfunction;
- 7. Major operations were performed within 28 days before enrollment, and minor
operations were performed within 14 days before enrollment;
- 8. Subjects who have received or are planning to receive allogeneic bone marrow
transplantation or solid organ transplantation;
- 9. Peripheral neuropathy = grade 2; Patients with active brain metastases, cancerous
meningitis, spinal cord compression, or diseases of the brain or pia meningiae found
by imaging CT or MRI examination at the time of screening (patients with brain
metastases who had completed treatment 14 days before enrollment and had stable
symptoms could be enrolled, but were confirmed to have no symptoms of cerebral
hemorrhage by craniocerebral MRI, CT or venography evaluation);
- 10. There are significant factors affecting oral drug absorption, such as inability to
swallow, chronic diarrhea, and the presence of clinically significant intestinal
obstruction.
- 11. Female subjects who are pregnant, breast-feeding, or planning to become pregnant
during the study period.
- 12. Patients with other serious physical or mental disorders or abnormal laboratory
tests that may increase the risk of study participation or interfere with study
results, and who are considered unsuitable for study participation by the
investigator.
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