Intrathecal Chemotherapy Through Ommaya Reservoir Upon Her-2 Negative Breast Cancer With Leptomeningeal Metastasis

Inclusion criteria

• Male or female aged 18 years or above;
• Can understand the purpose of clinical trials and the benefits and risks, voluntarily participate in and sign the informed consent
• The physical status score of the Eastern Oncology Consortium (ECOG) was ≤3;
• HER2-metastatic breast cancer confirmed histologically or cytologically (HER2- is defined as either a standard immunohistochemical (IHC) test result of 0 or 1+, or an IHC test result of 2+ and a negative ISH test result);
• Failure of standard treatment, or intolerance to standard treatment;
• pial metastasis is present, which is defined as meningeal metastasis confirmed by malignant tumor cells found in cerebrospinal fluid cytology; Or clinical symptoms/signs suggest meningeal metastasis, and brain MRI suggests pia enhancement;
• The function of major organs was good, which was confirmed by the following laboratory tests during the screening period:

Platelet count ≥80*10^9/L

Hemoglobin ≥8g/L

Neutrophil count ≥1.5*10^9/L

Serum creatinine ≤1.5*ULN

ALT and AST≤ 3*ULN (if liver metastases are present, ALT and AST≤5*ULN)

Serum total bilirubin ≤1.5*ULN

International Standardized ratio (INR) and Activated partial thromboplastin time (APTT) ≤1.5*ULN

• NYHA cardiac function grade ≤II, no obvious abnormality in ECG, or no clinical significance according to the investigators;
• Voluntary compliance with the trial protocol during the study period and regular follow-up;
• For all women of childbearing age, fertile men or their spouses who did not plan to have children or donate sperm during the entire trial period until 6 months after the last dose, or who voluntarily took effective contraception, the blood/urine pregnancy test results of female patients of childbearing age within 7 days before enrollment were negative.
• Subjects who have recovered from non-hematological toxicity from the last treatment (CTCAE≤ class 1, except for special conditions such as "alopecia") before first administration, and who the investigator determines that the corresponding AE does not pose a safety risk.

Exclusion criteria

• Pregnant or lactating women;
• Patients with acute and chronic infections, or with other serious diseases at the same time, were judged not suitable for this study;
• Other malignant tumors within 5 years (except the following cases: cured skin basal cell carcinoma, cervical carcinoma in situ, thyroid papillary carcinoma; A second primary cancer that has been eradicated and has not recurred within five years; Both primary cancers are expected to benefit from this study. Investigators have identified the primary tumor source of the metastases);
• Mental illness or mental disorder, poor compliance can not cooperate with and describe treatment response;
• There are serious organic diseases or major organ failure, such as decompensated heart and lung failure, which can not tolerate treatment;
• Patients with bleeding tendency;
• Patients who have received organ transplants;
• Patients taking adrenal corticosteroids or immunosuppressants for a long time;
• Intracranial hemorrhage unrelated to tumor disease;
• Patients with central nervous system complications requiring urgent treatment;
• Test group: subjects who could not collect CSF;
• The subject has a history of immunodeficiency, including HIV testing positive, or other acquired or congenital immunodeficiency diseases;
• Active viral hepatitis B (HBsAg positive with HBV DNA≥500 IU/mL) or hepatitis C. Among hepatitis C antibody positive subjects, only those whose polymerase chain reaction showed negative HCV RNA were eligible for enrollment (chronic hepatitis B or chronic hepatitis C patients with stable disease receiving standard antiviral therapy were eligible for enrollment);
• The subject has a serious cardiovascular clinical disease or symptom, including:

Congestive heart failure

History of unstable angina;

myocardial infarction within the past six months;

Clinically significant malignant arrhythmias (except atrial fibrillation and paroxysmal supraventricular tachycardia);

Subjects had clinically significant prolonged QTcF

High blood pressure that is not well controlled;

• The researcher believes that the patient has other conditions that are not suitable for participating in this study.