Osimertinib With Bevacizumab for Leptomeningeal Metastasis From EGFR-mutation Non-Small Cell Lung Cancer — OWBLM  

Non-small Cell Lung Cancer Clinical Trial

Official title: Phase II Study of Osimertinib With Bevacizumab for Leptomeningeal Metastasis From EGFR-mutation Non-Small Cell Lung Cancer

Status Recruiting

Clinical Trial Summary

Leptomeningeal metastasis (LM) is a fatal complication of advanced non-small cell lung cancer (NSCLC) associated with poor prognosis and rapid deterioration of performance status. The incidence of LM is increasing, reaching 3.8% in molecularly unselected NSCLC patients, being more frequent in adenocarcinoma subtype and up to 9% in epidermal growth factor receptor mutation (EGFRm) lung cancer patients, one-third of patients have concomitant brain metastasis . This increased incidence may in part be conducive to the increased survival of patients with EGFRm advanced NSCLC since the introduction of EGFR-tyrosine kinase inhibitions (TKIs).Currently, no standard therapeutic regimen for LM has been established because of its rarity and heterogeneity[11], and no approved therapies exists to specifically target LM in patients with EGFRm NSCLC. TKIs therapy is the first-line treatment of patients with EGFRm of NSCLC. The leptomeningeal space is a sanctuary site for tumour cells and therapeutic agents due to the presence of an active blood-brain barrier (BBB), so CSF concentration is an important factor affecting treatment of LM by TKIs. Standard-dose first- and second-generation EGFR-TKIs have good systemic efficacy but sub-optimal CNS penetration, as evidenced by preclinical studies of brain distribution and clinical reports of CSF penetration[15, 16]. Osimertinib is a third-generation EGFR-TKI, irreversible, oral EGFR-TKI that potently and selectively inhibits both EGFR-TKI sensitizing and EGFR T790M resistance mutations, which has demonstrated efficacy in NSCLC CNS metastasis[17-22]. Preclinical, I/II clinical studies and AURA program (AURA extension, AURA2, AURA17 and AURA3) have shown that Osimertinib has higher brain permeability than the first- and second-generation.

Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), animal studies and autopsy specimens show that VEGF plays an important role in LM. VEGF and EGFR share many overlapping and parallel downstream pathways. The biological rationale shows that inhibiting of EGFR and VEGR signaling pathways could improve the efficacy of antitumor and remove the resistance of EGFR inhibition. Besides, preclinical researches have shown the similar results. Based on these, numbers of clinical trials have confirmed that VEGF inhibitors in combination with EGFR-TKI significantly prolong patients' survival.

Clinical Trial Description

This is a phase II pilot study to evaluate the efficacy and safety of osimertinib with bevacizumab for LM from EGFRm NSCLC patients. ALL patients were treated with Osimertinib 80mg oral daily and bevacizumab 7.5mg/kg intravenous every 3 weeks. Study therapy continued until disease progression, unacceptable adverse event, or withdrawal of consent. ;

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• EGFR Activating Mutation
• Leptomeningeal Metastasis
• Lung Neoplasms
• Meningeal Carcinomatosis
• Neoplasm Metastasis
• Neoplasms, Second Primary
• Non-small Cell Lung Cancer

• NCT number: NCT04425681
• Study type: Interventional
• Source: Second Affiliated Hospital of Nanchang University
• Contact: Liu Anwen, Phd
• Phone: +8613767120022
• Email: awliu666@163.com
• Status: Recruiting
• Phase: Phase 2
• Start date: October 1, 2017
• Completion date: June 1, 2021