| Eligibility |
Inclusion Criteria:
- The age at the time of signing the informed consent form is = 18 years old and = 75
years old, for menopausal/premenopausal women (premenopausal women need to receive
ovarian function suppression treatment at the same time).
- Breast cancer patients with HR positive (ER expression = 10%, PR positive or negative)
and HER2 negative (Immunohistochemical(IHC)0,1+; 2+, Fluorescence in situ
hybridization(FISH) not expanded) confirmed by histology.
- Histologically confirmed locally advanced breast cancer (no radical local treatment)
or recurrent and metastatic breast cancer.
- The patients who had previously progressed after the treatment of first-line or
second-line cyclin-dependent kinases 4 and 6 inhibitors(CDK4/6 inhibitors)of endocrine
and whose chemotherapy was = second-line (relapse during the period of new
adjuvant/adjuvant treatment or within 12 months after the end of treatment was
regarded as first-line chemotherapy), the PIK3CA gene mutation detection was performed
a. PIK3CA Mutant subjects were enrolled in queue A; b. PIK3CA wild-type subjects were
included in queue B.
- At least one measurable primary lesion (according to RECIST v1.1 standard) before
enrollment.
- The Eastern Oncology Collaborative Group (ECOG) physical fitness score is 0-2.
- The toxic and side effects caused by previous anti-tumor therapy were relieved to 0-1
levels before the screening period (judged according to The NCI Common Terminology
Criteria for Adverse Events version5.0 (NCICTCAE5.0); except for toxicity that
researchers believe does not pose a safety risk to the subjects due to hair loss).
- The functional level of organs must meet the following requirements: 1) Blood routine:
Absolute neutrophil count(ANC)=1.5 × 109/L (growth factor not used within 14 days);
Platelet(PLT) =100 × 109/L (no corrective treatment used within 7 days); Hb = 100 g/L
(without corrective treatment within 7 days); 2) Blood biochemistry: Total bilirubin(TBIL)
=1.5 × upper limits of normal(ULN); Glutamine aminotransferase(ALT),Glutamic
transaminase(AST)=3 × ULN; Glutamine transpeptidase(GGT) =2.5 × ULN; If there is liver
metastasis, then ALT and/or AST = 5 × ULN; Glutamine transpeptidase GGT =5 × ULN; Urea,
Blood urea nitrogen (BUN), creatinine (Cr) =1.5 × ULN; 3) Cardiac ultrasound: Left
ventricular ejection fraction(LVEF)= 50%; 4) 12 lead ECG: QT interval (QTcF) corrected by
Fridericia method, male<450ms, female.
- Expected survival time = 3 months.
- Voluntarily participate in this clinical trial and sign a written informed consent
form.
Exclusion Criteria:
- Those who have received any mammalian target of rapamycin(mTOR) and histone
deacetylase(HDAC) inhibitors at any time in the past.
- Received chemotherapy, Targeted therapy, immunotherapy, interventional therapy or
other systematic anti-tumor treatment within 4 weeks before the first administration
of the study drug, or received radiotherapy within 3 weeks Note: Nitroso urea or
Mitomycin C is within 6 weeks before the first use of the study drug, oral
fluorouracil and small molecule targeted drugs are within 2 weeks before the first use
of the study drug or within 5 half lives of the drug (whichever is longer),
Traditional Chinese medicine with anti-tumor indications should be used within 2 weeks
before the first use of the study drug.
- Subjects who have undergone major surgical procedures or obvious trauma within 4 weeks
prior to enrollment, or are expected to undergo major surgical treatment.
- Subjects with brain or subdural metastasis are excluded. Unless its stability has been
maintained for at least 4 weeks or Asymptomatic brain metastasis can be included in
the group.
- According to the investigator's judgment, there are concomitant diseases (such as
severe hypertension, Thyroid disease, hyperlipidemia, active infection, etc.) that
seriously endanger the patient's safety or affect the patient's completion of the
study.
- Patients with poor control of diabetes shall be determined by the researcher.
- Clinically obvious gastrointestinal abnormalities that may affect drug intake,
transport or absorption (such as inability to swallow, chronic diarrhea, Bowel
obstruction, etc.).
- Severe cardiovascular injury (greater than a history of congestive heart failure at
New York Heart Association(NYHA) level II, unstable angina or myocardial infarction
within the past 6 months, or severe arrhythmia.
- Subjects have active hepatitis (hepatitis B reference: HBsAg positive and hepatitis B
virus(HBV) DNA = 500 international unit(IU)/ml; hepatitis C reference: hepatitis C
virus(HCV) antibody positive and HCV copy number>upper limit of normal value);
Subjects who are known to be positive for human immunodeficiency virus (HIV).
- Female patients during pregnancy and lactation, female patients with Fertility and
positive baseline Pregnancy test, or those of childbearing age who are unwilling to
take effective contraceptive measures during the whole test period and within 90 days
after the last administration of the study drug.
- Have a clear history of neurological or mental disorders, including epilepsy or
dementia, in the past.
- Any medical condition in which the researcher believes that the subject is not
suitable for entry into the study.
|
