Osimertinib With or Without Bevacizumab as Initial Treatment for Patients With EGFR-Mutant Lung Cancer

Stage IV Lung Cancer AJCC v8 Clinical Trial

Official title: Randomized Phase III Study of Combination Osimertinib (AZD9291) and Bevacizumab Versus Osimertinib (AZD9291) Alone as First-Line Treatment for Patients With Metastatic EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC)

Status Recruiting

Clinical Trial Summary

This phase III trial compares the effect of bevacizumab and osimertinib combination vs. osimertinib alone for the treatment of non-small cell lung cancer that has spread outside of the lungs (stage IIIB-IV) and has a change (mutation) in a gene called EGFR. The EGFR protein is involved in cell signaling pathways that control cell division and survival. Sometimes, mutations in the EGFR gene cause EGFR proteins to be made in higher than normal amounts on some types of cancer cells. This causes cancer cells to divide more rapidly. Osimertinib may stop the growth of tumor cells by blocking EGFR that is needed for cell growth in this type of cancer. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Giving osimertinib with bevacizumab may control cancer for longer and help patients live longer as compared to osimertinib alone.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To evaluate progression-free survival (PFS) of osimertinib (AZD9291) and bevacizumab versus osimertinib (AZD9291) alone as first-line treatment for patients with metastatic EGFR-mutant lung cancers.

SECONDARY OBJECTIVES:

I. To evaluate overall survival (OS). II. To evaluate best objective response rate and duration of objective response.

III. To evaluate time to central nervous system (CNS) progression and CNS PFS. IV. To evaluate toxicity of the combination regimen.

CORRELATIVE OBJECTIVES:

I. To characterize mechanisms of resistance to osimertinib (AZD9291) and osimertinib (AZD9291) with bevacizumab first-line therapy through post-progression circulating tumor-derived deoxyribonucleic acid (ctDNA).

II. To assess for ctDNA clearance on study treatment and associate ctDNA clearance with clinical outcomes.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive osimertinib orally (PO) once daily (QD) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive osimertinib PO QD on days 1-21 and bevacizumab intravenously (IV) over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients undergo echocardiography (ECHO), multigated acquisition scan (MUGA), computed tomography (CT) and may undergo magnetic resonance imaging (MRI) and blood sample collection on study.

After completion of study treatment, patients are followed up every 3 months for 10 years. ;

Related Conditions & MeSH terms

• Advanced Lung Non-Squamous Non-Small Cell Carcinoma
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Metastatic Lung Non-Squamous Non-Small Cell Carcinoma
• Recurrent Lung Non-Squamous Non-Small Cell Carcinoma
• Stage IIIB Lung Cancer AJCC v8
• Stage IV Lung Cancer AJCC v8

• NCT number: NCT04181060
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Recruiting
• Phase: Phase 3
• Start date: December 28, 2020
• Completion date: December 31, 2026