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Report for Clinical Trial NCT04148898

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Randomized Phase II Trial of Osimertinib Alone or in Combination With Bevacizumab for EGFR- Mutant Non-small Cell Lung Cancer With Leptomeningeal Metastasis

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

NCT04148898 Leptomeningeal Metastasis Non-small Cell Lung Cancer EGFR Activating Mutation
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung Neoplasm Metastasis Neoplasms, Second Primary Meningeal Carcinomatosis
HPO:Neoplasm of the lung Non-small cell lung carcinoma

2 Interventions

Name: Osimertinib

Description: Treatment of LM With osimertinb
Type: Drug
Group Labels: 2

osimertinb combined with bevacizumab group osimertinb group

Name: Bevacizumab

Description: Treatment of LM With osimertinb combined with bevacizumab
Type: Drug
Group Labels: 1

osimertinb combined with bevacizumab group


Primary Outcomes

Description: iPFS (Time from LM diagnosis to the first documentation of intracranial lesion progression or death with documented intracranial pro- gression,)

Measure: Intracranial progression-free

Time: Every 6 weeks, up to 2 years,

Description: ORR, proportion of patients with a best overall response of complete response or partial response (CR+PR)

Measure: Objective Response Rate

Time: Every 6 weeks, up to 2 years

Secondary Outcomes

Description: LM-OS defined as time from LM diagnosis to death due to any cause or last follow-up

Measure: LM Overall survival

Time: Every 3 weeks, up to 5 years,

Description: Proportion of patients progression-free by investigator assessment per RECIST v1.1

Measure: progression-free survival

Time: Every 6 weeks, up to 2 years,

Description: Number of patients with adverse events (AEs) as a measure of safety and tolerability

Measure: adverse events

Time: Every 3 weeks, up to 2 years,

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 T790M

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. --- T790M ---



HPO Nodes


HPO: