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

NCT06663306 | Recruiting Phase 1

• 1 other identifier: IS24103
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lung Cancer (NSCLC); Leptomeningeal Metastasis

Keywords

Leptomeningeal Metastases; NSCLC; Intrathecal Injection

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Overall Survival (OS)

  Up to 2 years

Other Outcomes (3)

• Clinical response rate

  Up to 2 years

• CSF cytology

  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

  From the beginning of the treatment until two months after the treatment.

Study Arms (2)

Arm A

EXPERIMENTAL

Enrolled patients were treated with pemetrexed intrathecal injection

Drug: Pemetrexed

Arm B

EXPERIMENTAL

Enrolled patients were treated with pemetrexed combined with bevacizumab intrathecal injection

Drug: Pemetrexed; Drug: Bevacizumab

Interventions

Pemetrexed DRUG

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

Arm A; Arm B

Bevacizumab DRUG

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.

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Shanghai Chest Hospital: lead
• Innovent Biologics (Suzhou) Co. Ltd.: collaborator

Study Sites (1)

Shanghai Chest Hospital

Shanghai, 200030, China

RECRUITING

Related Publications (1)

• 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 DERIVED

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Meningeal Carcinomatosis

Interventions

Pemetrexed; Bevacizumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Central Study Contacts

Hua Zhong, MD

CONTACT

+86 021-22200000; eddiedong8@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Respiratory Department

Study Record Dates

• First Submitted: October 24, 2024
• First Posted: October 29, 2024
• Study Start: December 9, 2024
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: March 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)