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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Leptomeningeal Metastasis; Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: Pemetrexed; Drug: Bevacizumab

• Study Type: Interventional
• Enrollment (Estimated): 19
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Hua Zhong, MD; Phone Number: +86 021-22200000; Email: eddiedong8@hotmail.com

Study Locations

• China
  • Shanghai, China, 200030
    • Recruiting
    • Shanghai Chest Hospital
    • Contact: Hua Zhong, MD; Phone Number: +86 021-22200000; Email: eddiedong8@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Enrolled patients were treated with pemetrexed intrathecal injection	Drug: Pemetrexed; Intrathecal pemetrexed 50mg,twice per week (d1, d8) for 1 week, then once per 4 weeks
Experimental: Arm B; Enrolled patients were treated with pemetrexed combined with bevacizumab intrathecal injection	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (Safety and Tolerability)	Number of participants with adverse events, treatment emergent adverse events,and serious adverse events assessed by CTCAE v5.0 as a measure of safety and tolerability.	From the beginning of the treatment until two months after the treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Kaplan-Meier method used to estimate the distribution of OS from the start of study treatment.	Up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response rate	The evaluation of clinical response rate was assessed by the investigators, which based on improvement of neurologic symptoms/signs and changes in the Karnofsky performance status score . This evaluation consists of five layers, including complete response (CR), obvious response (OR), partial response (PR), stable disease (SD) and progressive disease (PD).Clinical response was defined as the continuous presence of CR, OR or PR within an interval of at least 1 week. SD and PD were defined as ineffective.	Up to 2 years
CSF cytology	Cerebrospinal fluid (CSF) was collected before each cycle of intrathecal treatment, and assessed by the investigators the presence of tumor cells (Positive or Nagetive).	From the beginning of the intrathecal treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Radiographic assessment	Radiographic assessment with complete contrast-enhanced neuro-axis MRI or CT, Leptomeningeal metastases response was evaluated using the Response Assessment in Neuro-Oncology (RANO) criteria.	From the beginning of the treatment until two months after the treatment.

Collaborators and Investigators

• Sponsor: Shanghai Chest Hospital
• Collaborators: Innovent Biologics (Suzhou) Co. Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2024
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: October 24, 2024
• First Submitted That Met QC Criteria: October 26, 2024
• First Posted (Actual): October 29, 2024

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Leptomeningeal Metastases; Intrathecal Injection
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Nervous System Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Meningeal Neoplasms; Central Nervous System Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Meningeal Carcinomatosis; Amino Acids, Peptides, and Proteins; Proteins; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Bevacizumab; Pemetrexed
• Other Study ID Numbers: IS24103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual participant data that underlie the results reported in this study will be made available upon reasonable request from the corresponding author, subject to institutional review and applicable regulations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No