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

NCT ID: NCT06663306

Last Updated: 2024-10-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-30
• Study Completion Date: 2029-11-30

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

Enrolled patients were treated with pemetrexed intrathecal injection

Group Type: EXPERIMENTAL

Pemetrexed

Intervention Type: DRUG

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

Arm B

Enrolled patients were treated with pemetrexed combined with bevacizumab intrathecal injection

Group Type: EXPERIMENTAL

Pemetrexed

Intervention Type: DRUG

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

Bevacizumab

Intervention Type: 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.

Interventions

Pemetrexed

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

Intervention Type: 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.

Intervention Type: DRUG

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:

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Innovent Biologics (Suzhou) Co. Ltd.

INDUSTRY

Sponsor Role: collaborator

Shanghai Chest Hospital

OTHER

Sponsor Role: lead

Responsible Party

Hua Zhong

Chief of Respiratory Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Shanghai Chest Hospital

Shanghai, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Hua Zhong, MD

Role: CONTACT

eddiedong8@hotmail.com

+86 021-22200000

Facility Contacts

Hua Zhong, MD

Role: primary

eddiedong8@hotmail.com

+86 021-22200000

Other Identifiers

IS24103

Identifier Type: -

Identifier Source: org_study_id