Active Not Recruiting PHASE2 INTERVENTIONAL 2-arm NCT02971501

Osimertinib With or Without Bevacizumab in Treating Patients With EGFR Positive Non-small Cell Lung Cancer and Brain Metastases

A Phase II Trial of Osimertinib (AZD9291) With or Without Bevacizumab in Patients With EGFR Mutation Positive NSCLC and Brain Metastases

Sponsor: National Cancer Institute (NCI)

Conditions Metastatic Lung Non-Small Cell Carcinoma Metastatic Malignant Neoplasm in the Brain Stage IV Lung Cancer AJCC v8

Interventions Bevacizumab Biopsy Procedure Biospecimen Collection Computed Tomography Magnetic Resonance Imaging Osimertinib

Updated 62 times since 2017 Last updated: Dec 17, 2025 Started: Jun 27, 2018 Primary completion: Feb 18, 2025 Completion: Jul 1, 2026

This information is for research purposes only and is not medical advice. Consult a healthcare provider before making any medical decision.

A PHASE2 clinical study on Metastatic Lung Non-Small Cell Carcinoma and Metastatic Malignant Neoplasm in the Brain, this trial is ongoing. The trial is conducted by National Cancer Institute (NCI) and has accumulated 62 data snapshots since 2018. Oncology trials at this stage typically focus on safety, tolerability, and early efficacy signals.

Study Description(click to expand)

PRIMARY OBJECTIVE: I. To determine the progression-free survival with osimertinib (AZD9291) plus bevacizumab compared to osimertinib (AZD9291) alone. SECONDARY OBJECTIVES: I. To assess the safety and tolerability of the combination of osimertinib (AZD9291) and bevacizumab. II. To evaluate the time to progression in the central nervous system (CNS) with osimertinib (AZD9291) plus bevacizumab versus single-agent osimertinib (AZD9291). III. To determine the overall response rate and the intracranial response rate to the combination versus single agent. IV. To assess the overall survival in patients receiving osimertinib (AZD9291) plus bevacizumab compared to osimertinib (AZD9291) alone. TRANSLATIONAL OBJECTIVES: I. To investigate mechanisms of sensitivity and resistance to combination osimertinib (AZD9291) plus bevacizumab versus osimertinib (AZD9291) by molecularly characterizing tumor samples including T790M status. II. To assess whether circulating tumor deoxyribonucleic acid (DNA) in plasma can be used as an indicator of sensitivity and resistance to treatment. III. To determine whether an angiogenic signature using a multiplex panel array is associated with benefit from the combination of osimertinib (AZD9291) plus bevacizumab. IV. To investigate angiogenesis, immune and signaling pathway markers in tumor samples to determine biomarkers predictive of benefit from combination therapy. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients...

PRIMARY OBJECTIVE:

I. To determine the progression-free survival with osimertinib (AZD9291) plus bevacizumab compared to osimertinib (AZD9291) alone.

SECONDARY OBJECTIVES:

I. To assess the safety and tolerability of the combination of osimertinib (AZD9291) and bevacizumab.

II. To evaluate the time to progression in the central nervous system (CNS) with osimertinib (AZD9291) plus bevacizumab versus single-agent osimertinib (AZD9291).

III. To determine the overall response rate and the intracranial response rate to the combination versus single agent.

IV. To assess the overall survival in patients receiving osimertinib (AZD9291) plus bevacizumab compared to osimertinib (AZD9291) alone.

TRANSLATIONAL OBJECTIVES:

I. To investigate mechanisms of sensitivity and resistance to combination osimertinib (AZD9291) plus bevacizumab versus osimertinib (AZD9291) by molecularly characterizing tumor samples including T790M status.

II. To assess whether circulating tumor deoxyribonucleic acid (DNA) in plasma can be used as an indicator of sensitivity and resistance to treatment.

III. To determine whether an angiogenic signature using a multiplex panel array is associated with benefit from the combination of osimertinib (AZD9291) plus bevacizumab.

IV. To investigate angiogenesis, immune and signaling pathway markers in tumor samples to determine biomarkers predictive of benefit from combination therapy.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive osimertinib orally (PO) once daily (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.

ARM II: Patients receive osimertinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI), tumor biopsy and blood sample collection throughout the study.

After completion of study treatment, patients are followed up for a minimum of 4 weeks.

Status Flow

Change History

62 versions recorded

Jan 2026 — Present [monthly]

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First recorded

Eligibility Summary

No eligibility information available.

Contact Information

Sponsor contact:

National Cancer Institute (NCI)

Data source: National Cancer Institute (NCI)

For direct contact, visit the study record on ClinicalTrials.gov .

Study Locations

Bellevue, United States , Columbus, United States , Fairway, United States , Los Angeles, United States , New Haven, United States , New York, United States , Oklahoma City, United States , Omaha, United States , Pasadena, United States , Pittsburgh, United States and 4 more locations