ClinicalTrials.Veeva

Menu

Osimertinib With or Without Bevacizumab for EGFR- Mutant Non-small Cell Lung Cancer With Leptomeningeal Metastasis (OWONBNSCLCLM)

N

Nanchang University

Status and phase

Unknown
Phase 2

Conditions

Leptomeningeal Metastasis
EGFR Activating Mutation
Non-small Cell Lung Cancer

Treatments

Drug: Bevacizumab
Drug: Osimertinib

Study type

Interventional

Funder types

Other

Identifiers

NCT04148898
YC2019-S087

Details and patient eligibility

About

Leptomeningeal metastasis (LM) is a devastating and terminal complication of advanced non-small-cell lung cancer (NSCLC), especially in patients harboring epidermal growth factor receptor (EGFR) mutations. Osimertinib is an oral,third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations .AURA I/II study and other preclinical study suggested that Osimertinib exhibited a better blood-brain barrier(BBB) penetration than the other EGFR-TKIs (gefitinib, erlotinib, or afatinib).The BLOOM 、AURA and FLURA study demonstrated that osimertinib showed encouraging activity and manageable tolerability in pretreated EGFR-mutant NSCLC patients with LM. Bevacizumab is a monoclonal antibody against vascular endothelial growth factor (VEGF). Animal study and autopsy specimens showed that VEGF is an essential factor in LM. Recently study showed EGFR-TKIs plus bevacizumab prolonged PFS and OS in patients with EGFR-mutant NSCLC and multiple brain mteastasis when compared with EGFR-TKIs alone. Howerver osimertinib combined with bevacizumab could benefit patients with LM from EGFR- mutant NSCLC remains undetermined. Therefore, the purpose of the study is to evaluate the safety and efficacy of osimertinib combined with bevacizumab for EGFR- mutant non-small cell lung cancer with leptomeningeal metastasis

Full description

This is a randomized phase II clinical trial. The objective of the study is to assess the efficacy of osimertinib combined with bevacizumab for LM from EGFR- mutant NSCLC. Patients were randomized with equal allocation to 80 mg of oral Osimertinib daily alone or with 7.5 mg/kg of intravenous bevacizumab every 3 weeks. Study therapy continued until disease progression, unacceptable adverse event, or withdrawal of consent

Enrollment

80 estimated patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Age in 18-80 years
  • Pathologically proven NSCLC
  • EGFR mutation , the EGFR status was identified from primary lung tumors using the amplification refractory mutation system (ARMS) or next-generation sequencing (NGS) analysis.
  • LM diagnosis was based on the detection of malignant cells in the CSF, the focal or diffuse enhancement of leptomeninges, and nerve roots or the ependymal surface on gadolinium-enhanced MRI .
  • No severe abnormal liver and kidney function;
  • No other severe chronic diseases;
  • Signed informed consent form

Exclusion criteria

  • Patients with the clinical manifestation of nervous system failure including severe encephalopathy, grade III-IV white matter lesions confirmed by imaging examination, moderate or severe coma, and glasgow coma score less than 9 points;
  • Allergic to osimertinib or bevacizumab
  • Any of the following: Pregnant women ;Nursing women ;Men or women of childbearing potential who are unwilling to employ adequate contraception
  • History of myocardial infarction or other evidence of arterial thrombotic disease (angina), symptomatic congestive heart failure (New York Heart Association ≥ grade 2), unstable angina pectoris, or cardiac arrhythmia; Note: allowed only if patient has no evidence of active disease for at least 6 months prior to randomization;
  • History of cerebral vascular accident (CVA) or transient ischemic attack (TIA)≤ 6 months prior to randomization
  • History of bleeding diathesis or coagulopathy
  • History of hemoptysis da≥ grade 2 (defined as bright red blood of at least 2.5 mL) ≤3 months prior to randomization
  • Leukocytes below 2*10^9/L, neutrophils below 1*10^9/L; platelets below 50*10^9/L;
  • Had major surgery within 60 days;
  • History of arteriovenous thrombosis
  • Gastrointestinal perforator in the past 6 months
  • Inadequately controlled hypertension (systolic blood pressure of > 150 mmHg or diastolic pressure > 100 mmHg on anti-hypertensive medications); Note: history of hypertensive crisis or hypertensive encephalopathy not allowed
  • Grade 4 proteinuria

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Single Blind

80 participants in 2 patient groups

osimertinb group
Experimental group
Description:
Osimertinib 80 mg oral daily
Treatment:
Drug: Osimertinib
osimertinb combined with bevacizumab group
Experimental group
Description:
Osimertinib 80 mg oral daily; .bevacizumab 7.5 mg/kg intravenous every 3 weeks
Treatment:
Drug: Osimertinib
Drug: Bevacizumab

Trial contacts and locations

0

Loading...

Central trial contact

Liu Anwen, Phd; Cai Jing, Phd

Data sourced from clinicaltrials.gov

Clinical trials

Find clinical trialsTrials by location
© Copyright 2025 Veeva Systems