non-small cell lung cancer
Conditions
Interventions
experimental group:Intrathecal injection of immune drugs
Sponsors
Huashan Hospital Affiliated to Fudan University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1: Age > 18 years old, gender not restricted; 2: Pathologically diagnosed as non-small cell lung cancer, and confirmed as leptomeningeal metastasis by cerebrospinal fluid cytology; 3: No restrictions on the previous anti-tumor treatment regimens (such as immunotherapy, chemotherapy, targeted drugs, anti-angiogenesis, traditional Chinese medicine, etc.) used by patients with leptomeningeal metastasis. All can be included; 4: All patients with leptomeningeal metastasis have developed resistance to standard treatment and have failed at least one intrathecal injection drug treatment. For non-squamous NSCLC patients, EGFR/ALK/ROS1 and other driver gene status must be confirmed by genetic testing. For patients with positive driver genes, the following conditions must be met: a. For patients with EGFR-TKI resistance, further genetic testing is required; if other driver gene mutations are positive (such as MET, RET, etc.), resistance to TKI treatment targeting that target is required before inclusion; for patients with resistance to first-generation EGFR-TKI and T790M mutation, resistance to third-generation EGFR-TKI is required. b. For patients with other positive driver genes, resistance to available targeted drugs is required; 5: ECOG performance status score of 0-2; patients with a score of 3-4 due to neurological symptoms caused by leptomeningeal metastasis are allowed to be included; 6: Expected survival time of at least 4 weeks; 7: Previous radiotherapy, including whole brain radiotherapy, stereotactic radiosurgery or stereotactic body radiotherapy (SBRT), must be completed at least 7 days before the start of treatment; 8: Concurrent intrathecal treatment with other drugs is not allowed; 9: Laboratory test indicators meet the following standards: a. Bone marrow function: hemoglobin (Hb) > 80g/L; white blood cell count (WBC) > lower limit of normal; absolute neutrophil count (ANC) > 1.5x10^9/L; platelet count > 70x10^9/L. b. Renal function: creatinine (Cr) 55 ml/min. c. Liver function: total bilirubin <= 1.5 times ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 times ULN; (if there is liver metastasis, total bilirubin should not exceed 3 times the normal upper limit, and transaminase should not exceed 5 times the normal upper limit). d. Coagulation function: international normalized ratio (INR) of prothrombin time < 1.5 times ULN, partial thromboplastin time <= 1.5 times ULN; for subjects receiving prophylactic anticoagulation treatment, the investigator will determine whether INR and APTT are within the safe and effective treatment range; 10: Patients with a history of ventriculoperitoneal shunt can receive intrathecal injection treatment through a ventricular device with a self-closing valve, and patients with Ommaya reservoirs can receive intrathecal injection through the Ommaya reservoir; 11: Women of childbearing age agree to take contraceptive measures during the study and for 6 months after the study; negative pregnancy test (serum or urine) within 7 days before enrollment, and not in the lactation period; men agree to take contraceptive measures during the study and for 6 months after the study; 12: No participation in other drug clinical trials within 4 weeks before enrollment; 13: The subject can understand the study situation and voluntarily sign the informed consent form; it is exp
Exclusion criteria
Exclusion criteria: 1: Patients with conditions related to cancer or meningeal diseases requiring urgent intervention, who have not received clinical management or stabilization before enrollment; 2: Respiratory syndrome (>=CTCAE grade 2 dyspnea), uncontrolled serous cavity effusion (including pleural effusion, ascites, pericardial effusion); 3: Unable to undergo enhanced craniospinal magnetic resonance imaging (MRI); 4: Other differential diagnoses for excluding leptomeningeal metastasis: a. Aseptic meningitis b. Viral meningitis c. Bacterial meningitis; 5: Acute phase of high cervical spinal cord tumors or spinal cord trauma. Patients with obstructive hydrocephalus; 6: Central nervous system infectious diseases; patients who have undergone lumbar puncture and intrathecal injection treatment, with local infection, hematoma, open injury, or spinal tuberculosis at the lumbar puncture site; 7: Severe encephalopathy, grade III-IV white matter lesions confirmed by imaging; 8: Patients with unstable systemic diseases, including but not limited to: severe infection, uncontrolled diabetes, unstable angina pectoris, cerebrovascular accident or transient ischemic attack, myocardial infarction, congestive heart failure, severe arrhythmia requiring drug treatment, liver, kidney or metabolic diseases. 9: Patients with any active autoimmune diseases or a history of autoimmune diseases, including but not limited to: interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism or hypopituitarism (patients on hormone replacement therapy may be considered for inclusion); patients with psoriasis only requiring topical ointment and not affecting quality of life or childhood asthma/allergy completely relieved and no intervention required in adulthood may be considered for inclusion, but patients requiring medical intervention with bronchodilators cannot be included; 10: Patients who have experienced grade 3 or higher autoimmune-related adverse reactions during previous PD-1/PD-L1 immunotherapy; 11: Cachexia; 12: Uncontrolled epileptic seizures, neurological dysfunction, or severe neurological damage related to treatment; 13: Severe trauma or surgery within 1 month before enrollment; 14: Live or attenuated vaccines for infectious disease prevention within 30 days before enrollment (injection-type seasonal influenza vaccines are allowed); 15: Allergy history to siltuximab or any of its components or contraindications to treatment; 16: Individuals deemed unsuitable for enrollment by the investigator. Such as patients with diseases (such as mental illness, etc.) or conditions (such as alcoholism or drug abuse, etc.) that increase the risk of patients receiving the investigational drug or affect their compliance with the trial requirements, or may confuse the research results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The incidence of adverse events of grade 3 or higher according to CTCAE;Maximum tolerated dose(MTD);dose-limiting toxicity(DLT);Determine the recommended phase II dosage(PR2D); | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival (OS);Intracranial objective response rate(iORR);Intracranial Progression-free survival (iPFS); | — |
Countries
China
Contacts
Public ContactXinli Zhou
Huashan Hospital Affiliated to Fudan University
Outcome results
None listed