NCT04148898: OWONBNSCLCLM

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

Status unknown Phase 2 Last updated 4 November 2019

What this trial tests

Phase 2 trial testing Osimertinib in Leptomeningeal Metastasis in 80 participants. Status unknown.

Timeline

1 November 2019

Primary endpoint
1 March 2021

1 July 2021

Quick facts

Lead sponsor	Second Affiliated Hospital of Nanchang University
Phase	Phase 2
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	80
Start date	1 November 2019
Primary completion	1 March 2021
Estimated completion	1 July 2021

Drugs / interventions tested

• Osimertinib (osimertinib) — full drug profile →
• Bevacizumab (Bevacizumab-Bvzr) — full drug profile →

Conditions studied

• Leptomeningeal Metastasis — all drugs for Leptomeningeal Metastasis →
• Non-small Cell Lung Cancer — all drugs for Non-small Cell Lung Cancer →
• EGFR Activating Mutation — all drugs for EGFR Activating Mutation →

Sponsor

Second Affiliated Hospital of Nanchang University

Who can join

Adults 18 to 80, any sex, with Leptomeningeal Metastasis or Non-small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Treatment Strategies for Non-Small Cell Lung Cancer with Common <i>EGFR</i> Mutations: A Review of the History of EGFR TKIs Approval and Emerging Data.
   Marin-Acevedo JA, Pellini B, Kimbrough EO, Hicks JK, et al · · 2023 · cited 35× · PMID 36765587 · DOI 10.3390/cancers15030629
2. Leptomeningeal Metastases from Solid Tumors: Recent Advances in Diagnosis and Molecular Approaches.
   Pellerino A, Brastianos PK, Rudà R, Soffietti R. · · 2021 · cited 32× · PMID 34207653 · DOI 10.3390/cancers13122888
3. Osimertinib in EGFR-Mutated Lung Cancer: A Review of the Existing and Emerging Clinical Data.
   Lee CS, Milone M, Seetharamu N. · · 2021 · cited 24× · PMID 34471361 · DOI 10.2147/ott.s227032
4. Potential benefit of osismertinib plus bevacizumab in leptomeningeal metastasis with EGFR mutant non-small-cell lung cancer.
   Yi Y, Cai J, Xu P, Xiong L, et al · · 2022 · cited 20× · PMID 35287683 · DOI 10.1186/s12967-022-03331-9
5. Challenges and Advances in Diagnosis and Treatment of Leptomeningeal Disease (LMD).
   Ferguson SD, Fomchenko EI, Guerrieri RA, Glitza Oliva IC. · · 2021 · cited 20× · PMID 35096602 · DOI 10.3389/fonc.2021.800053
6. Subsequent treatments beyond progression on osimertinib in EGFR-mutated NSCLC and leptomeningeal metastases.
   Zheng MM, Li YS, Tu HY, Sun H, et al · · 2022 · cited 12× · PMID 35644609 · DOI 10.1186/s12916-022-02387-0
7. A Comprehensive Review of Contemporary Literature for Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer and Their Toxicity.
   Lee CS, Sharma S, Miao E, Mensah C, et al · · 2020 · cited 8× · PMID 33117017 · DOI 10.2147/lctt.s258444
8. Comparison of osimertinib plus bevacizumab against osimertinib alone in NSCLC harboring EGFR mutations: a systematic review and meta-analysis.
   Zhou G, Guo L, Xu J, Tang K, et al · · 2024 · cited 7× · PMID 38304850 · DOI 10.1177/17588359241227677