| Eligibility |
Inclusion Criteria:
1. Patient is = 18 years old at the time of signing the informed consent form.
2. Eastern Cooperative Oncology Group (ECOG) performance status =2.
3. HER2-positive: In the pathological examination/rechecking of primary lesions or
metastatic lesions performed by the Research site's Pathology Laboratory, at least
once the tumor cells defined as 3+ staining by immunohistochemistry, or fluorescence
in situ hybridization [FISH] confirmed positive
4. MRI/enhanced CT confirmed brain metastasis. According to RECIST 1.1, there is at least
one measurable brain lesion, and the measurability of extracranial lesions is not
required
5. Patients Group Cohort A: participants with brain metastases who have not previously
been treated with CNS radiotherapy, it should be more than two weeks since the end of
the last systemic treatment. Patients with new brain lesions after craniotomy are
allowed to be included, provided that they have not received radiotherapy after
surgery and are at least 2 weeks away from surgery.
Cohort B: Patients with disease progression or new lesions after whole brain
radiotherapy (WBRT) or stereotactic radiotherapy (SRT); For lesions that have received
local treatment, there is clear evidence of progress in imaging examination, and the
lesions that have undergone radiotherapy can be selected as target lesions. If a
patient has multiple CNS lesions, only one or a few of which are treated with SRT, and
there are lesions that are not treated locally, such patients are still eligible for
enrollment in this study.
6. Previous treatment
Acceptable previous treatments:
History of trastuzumab and other anti-HER2 macromolecular antibodies. Any lines of
previous chemotherapy. History of endocrine therapy. Patients who have not used
capecitabine except for patients with progression at least 6 (for metastatic disease)
or 12 (as adjuvant therapy) months after discontinuation of a capecitabine-containing
treatment.
Concurrent use of bisphosphonates, mannitol and glucocorticoids is allowed, provided
that the dosage(?2 mg dexamethasone (or equivalent) per day) of glucocorticoids is
stable for at least one week before enrollment.
7. Expected to survival = 6 months
8. Patients must have adequate organ function, criteria as follows.
1. Blood routine examination:Absolute Neutrophil Count (ANC)=1.0×109/L; PLT
=100×109/L; Hb =90g/L
2. Blood chemistry test:TBIL =1.5 times the upper limit of normal (ULN); ALT and
AST=3 times ULN; For patients with liver metastases, ALT and AST=5×ULN; BUN and
Cr=1×ULN and creatinine clearance =50mL/min (CockcroftGault formula);
3. Ultrasonic cardiogram: LVEF=50%
4. 12-lead ECG: The QT interval (QTcF) corrected by Fridericia's method is < 450
ms/man and < 470 ms/women.
9. Patients need to voluntarily join this study after they fully understand and sign the
informed consent form. Patients need to have good compliance and be willing to
cooperate with follow-up.
Exclusion Criteria:
1. Patients with leptomeningeal metastasis (diagnosed by imaging/positive cerebrospinal
fluid cytology) or a clear indication of clinically significant leptomeningeal
involvement;
2. CNS complications that require urgent neurosurgical intervention (e.g. resection,
shunt placement). Patients with poorly response brain metastases after dehydration
treatment and glucocorticoid treatment. Such as uncontrollable increase in
intracranial pressure, jet vomiting, mental disorders, epilepsy, cognitive impairment,
etc.
3. Third space fluid that cannot be controlled by drainage or other methods (such as
large amounts of pleural fluid and ascites);
4. Patients who have received chemotherapy, surgery or molecular targeted therapy within
2 weeks before enrollment; patients who have received endocrine therapy within 1 week
before enrollment; minor surgery, such as tumor biopsy, thoracentesis or intravenous
catheterization or the like are allowed;
5. Participated in other clinical trial within 4 weeks prior to randomization.
6. Concurrent treated, or who has been treated with HER2 tyrosine kinase inhibitors
(including lapatinib, neratinib, pyrotinib, etc.);
7. History of other malignant tumors within 5 years, excluding cured cervical carcinoma
in situ, skin basal cell carcinoma or skin squamous cell carcinoma;
8. Receiving any other anti-tumor therapies at time of study screening visit.
9. There are serious and/or uncontrolled complications that may affect participation,
including any of the following:
1. dysphagia, chronic diarrhea and intestinal obstruction and factors that affect
the administration and absorption of the drug;
2. Allergic constitution; Allergic to the study drug; History of immunodeficiency,
including HIV positive, or other acquired or congenital immunodeficiency
diseases; History of organ transplantation;
3. History of severe heart disease, including: myocardial infarction and heart
failure; any other heart disease that is not suitable for participation
(investigator assessment);
4. Infection.
10. Female patients during pregnancy and lactation; fertile female patients who tested
positive on a baseline pregnancy test; female patients of childbearing age who are
unwilling to take effective contraceptive measures during the trial.
11. Any other circumstances that are not suitable for inclusion in this study
(investigator assessment)
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