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

Официальное название

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

Обзор

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (1)

• Overall Survival (OS) [Срок оценки: Up to 2 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shanghai Chest Hospital — Шанхай

Публикации

• 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

Идентификаторы

NCT: NCT06663306 · IS24103

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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