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

Shanghai Jiao Tong University

Status and phase: Enrolling; Phase 1

Conditions: Leptomeningeal Metastasis; Lung Cancer (NSCLC)

Treatments: Drug: Bevacizumab; Drug: Pemetrexed

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06663306

IS24103

Details and patient eligibility

About

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.

Enrollment: 19 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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19 participants in 2 patient groups

Arm A

Experimental group

Description:

Enrolled patients were treated with pemetrexed intrathecal injection

Treatment:

Drug: Pemetrexed

Arm B

Experimental group

Description:

Enrolled patients were treated with pemetrexed combined with bevacizumab intrathecal injection

Treatment:

Drug: Pemetrexed

Drug: Bevacizumab