Intrathecal treatment for lung cancer with leptomeningeal metastases

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

This study is testing a new way to deliver two cancer drugs directly into the spine to see if it helps people with lung cancer that has spread to the brain and who haven't responded well to other treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 19 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shanghai Chest Hospital (Academic / other)
• Drugs / interventions: bevacizumab, radiation
• Locations: 1 site (Shanghai)
• Trial ID: NCT06663306 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of combining Pemetrexed and Bevacizumab delivered via intrathecal injection in patients suffering from leptomeningeal metastases due to non-small cell lung cancer (NSCLC). It is a prospective, single-arm, phase 1 study aimed at patients who have shown inadequate response to standard systemic treatments. The study will assess the impact of this novel approach on disease progression and neurological symptoms associated with leptomeningeal metastases.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with pathologically confirmed NSCLC and diagnosed leptomeningeal metastases who have not responded adequately to standard treatments.

Not a fit: Patients with leptomeningeal metastases who are not experiencing disease progression or neurological decline while on standard systemic treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with leptomeningeal metastases in NSCLC, potentially improving their quality of life and survival outcomes.

How similar studies have performed: While this approach is novel, similar studies targeting leptomeningeal metastases have shown promise, indicating potential for success.

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.

Where this trial is running

Shanghai

• Shanghai Chest Hospital — Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Hua Zhong, MD

Conditions Lung Cancer; Leptomeningeal Metastasis; Leptomeningeal Metastases; NSCLC; Intrathecal Injection