Clinical Trial Finder

Inclusion Criteria:

• - Age ≥ 18 years; - ECOG PS score 0-3.

ECOG PS score 2 or 3 should be due to leptomeningeal metastases.

• - Patients with pathologically diagnosed non-small cell lung cancer with cerebrospinal fluid and/or MRI diagnosis of leptomeningeal metastasis(LM); - Unsatisfactory efficacy of LM,which defined as disease progression in LM,or LM-related neurological progression, while patients received standard systemic anti-tumor treatment; - Expected survival time ≥ 1 month; - The laboratory test results meet the following criteria:Hemoglobin ≥ 90 g/L, neutrophil count ≥ 1.5 × 10^9/L, platelet count ≥ 100 × 10^9/L; Total bilirubin ≤ 1.5 times the upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN ; Creatinine≤ 2.0 × ULN,or Creatinine clearance rate (CrCl) ≥ 50 mL/min; - Females of child-bearing potential agree to use contraception during the study period and for 6 months after the completion of the study; patients who have had a negative serum or urine pregnancy test within seven days prior to enrollment in the study and who are not breastfeeding; and males agreeing to use contraception during the study period and for 6 months after the completion of the study; - Understand and sign the informed consent form.

Exclusion Criteria:

• - Positive for human immunodeficiency virus (HIV) ; - History of allergy to pemetrexed or bevacizumab; - History of pemetrexed and/or bevacizumab intrathecal Injection; - Presence of contraindication of bevacizumab: 1.

Uncontrolled hypertension(systolic pressure≥150mmHg，or diastolic pressure≥100mmHg；History of hypertensive crisis or hypertensive encephalopathy; 2. Urine protein≥2+,or 24-hour urine protein≥2g； 3. Unstable angina pectoris, symptomatic congestive heart failure,myocardial infarction within 6 months before enrollment, severe vascular disease, severe uncontrolled arrhythmia; 4. Major hemoptysis within the past 1 month; History of coagulation disorders; 5. Presence of serious non-healing wounds, ulcers, or bone fractures. 6. Presence of abdominal fistula, gastrointestinal perforation, or gastrointestinal tract obstruction; 7. Presence of macrovascular invasion； 8. Some neurological disorders unrelated to tumors，such as intracranial infection,cerebral hemorrhage,cerebral infarction,encephalitis;

• - Brain/spinal cord radiation therapy within 1 week before enrollment; - Pregnant and lactating female; - Refuse to use contraception during the study period; - Individuals considered by the investigator to be unsuitable for enrollment.

Arms

Experimental: Arm A

Enrolled patients were treated with pemetrexed intrathecal injection

Experimental: Arm B

Enrolled patients were treated with pemetrexed combined with bevacizumab intrathecal injection

Interventions

Drug: - Pemetrexed

Intrathecal pemetrexed 50mg,twice per week (d1, d8) for 1 week, then once per 4 weeks

Drug: - Bevacizumab

Intrathecal bevacizumab, once (d8)for 1 week, then once per 4 weeks.The initial dose of intrathecal bevacizumab is 5 mg, escalated to 10 mg, and then 25 mg, and then 37.5mg, and then 50mg.