Intrathecal Injection Pemetrexed And Bevacizumab in Patients With Leptomeningeal Metastases in NSCLC

Official title

Efficacy and Safety of Pemetrexed Combined With Bevacizumab Intrathecal Injection in Patients With Leptomeningeal Metastases in NSCLC

Overview

This is a prospective, single-arm, phase Ia clinical study, which was designed to evaluate the efficacy and safety of Pemetrexed Combined With Bevacizumab Intrathecal Injection in Patients With Leptomeningeal Metastases in NSCLC.

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.

Primary outcome measures

• Incidence of Adverse Events (Safety and Tolerability) [Time frame: From the beginning of the treatment until two months after the treatment.]

Secondary outcome measures (1)

• Overall Survival (OS) [Time frame: Up to 2 years]

Eligibility criteria

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:

• Uncontrolled hypertension(systolic pressure≥150mmHg，or diastolic pressure≥100mmHg；History of hypertensive crisis or hypertensive encephalopathy;
• Urine protein≥2+,or 24-hour urine protein≥2g；
• Unstable angina pectoris, symptomatic congestive heart failure,myocardial infarction within 6 months before enrollment, severe vascular disease, severe uncontrolled arrhythmia;
• Major hemoptysis within the past 1 month; History of coagulation disorders;
• Presence of serious non-healing wounds, ulcers, or bone fractures
• Presence of abdominal fistula, gastrointestinal perforation, or gastrointestinal tract obstruction;
• Presence of macrovascular invasion；
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai Chest Hospital — Shanghai

Publications

• Kuang Y, Teng J, Wang W, Zhang B, Cheng L, Zhang Y, Liu W, Gao Z, Nie W, Xiong L, Shi C, Zhang W, Lou Y, Han B, Zhong H. Safety and efficacy of intrathecal pemetrexed and bevacizumab in non-small cell lung cancer (NSCLC) patients with leptomeningeal metastases (LM): protocol for a single-arm, prospective, phase Ia trial. BMJ Open. 2026 Mar 23;16(3):e116187. doi: 10.1136/bmjopen-2026-116187. PMID 41877338

Identifiers

NCT: NCT06663306 · IS24103

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗