Leptomeningeal Metastasis, Lung Cancer (NSCLC)
Conditions
Keywords
Leptomeningeal Metastases, NSCLC, Intrathecal Injection
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.
Interventions
DRUGPemetrexed
Intrathecal pemetrexed 50mg,twice per week (d1, d8) for 1 week, then once per 4 weeks
DRUGBevacizumab
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.
Sponsors
Shanghai Chest Hospital
Innovent Biologics (Suzhou) Co. Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events (Safety and Tolerability) | From the beginning of the treatment until two months after the treatment. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to 2 years | Kaplan-Meier method used to estimate the distribution of OS from the start of study treatment. |
Countries
China
Contacts
CONTACTHua Zhong, MD
Outcome results
None listed