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

November 1, 2019 updated by: Second Affiliated Hospital of Nanchang University

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

This is a randomized phase II clinical trial. The objective of the study is to assess the efficacy of osimertinib combined with bevacizumab for LM from EGFR- mutant NSCLC. Patients were randomized with equal allocation to 80 mg of oral Osimertinib daily alone or with 7.5 mg/kg of intravenous bevacizumab every 3 weeks. Study therapy continued until disease progression, unacceptable adverse event, or withdrawal of consent

Study Type

Interventional

Enrollment (Anticipated)

80

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age in 18-80 years
  • Pathologically proven NSCLC
  • EGFR mutation , the EGFR status was identified from primary lung tumors using the amplification refractory mutation system (ARMS) or next-generation sequencing (NGS) analysis.
  • LM diagnosis was based on the detection of malignant cells in the CSF, the focal or diffuse enhancement of leptomeninges, and nerve roots or the ependymal surface on gadolinium-enhanced MRI .
  • No severe abnormal liver and kidney function;
  • No other severe chronic diseases;
  • Signed informed consent form

Exclusion Criteria:

  • Patients with the clinical manifestation of nervous system failure including severe encephalopathy, grade III-IV white matter lesions confirmed by imaging examination, moderate or severe coma, and glasgow coma score less than 9 points;
  • Allergic to osimertinib or bevacizumab
  • Any of the following: Pregnant women ;Nursing women ;Men or women of childbearing potential who are unwilling to employ adequate contraception
  • History of myocardial infarction or other evidence of arterial thrombotic disease (angina), symptomatic congestive heart failure (New York Heart Association ≥ grade 2), unstable angina pectoris, or cardiac arrhythmia; Note: allowed only if patient has no evidence of active disease for at least 6 months prior to randomization;
  • History of cerebral vascular accident (CVA) or transient ischemic attack (TIA)≤ 6 months prior to randomization
  • History of bleeding diathesis or coagulopathy
  • History of hemoptysis da≥ grade 2 (defined as bright red blood of at least 2.5 mL) ≤3 months prior to randomization
  • Leukocytes below 2*10^9/L, neutrophils below 1*10^9/L; platelets below 50*10^9/L;
  • Had major surgery within 60 days;
  • History of arteriovenous thrombosis
  • Gastrointestinal perforator in the past 6 months
  • Inadequately controlled hypertension (systolic blood pressure of > 150 mmHg or diastolic pressure > 100 mmHg on anti-hypertensive medications); Note: history of hypertensive crisis or hypertensive encephalopathy not allowed
  • Grade 4 proteinuria

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: osimertinb group
Osimertinib 80 mg oral daily
Drug: Osimertinib
Treatment of LM With osimertinb
Other Names:
  • AZD9291
Experimental: osimertinb combined with bevacizumab group

Osimertinib 80 mg oral daily;

.bevacizumab 7.5 mg/kg intravenous every 3 weeks
Drug: Osimertinib
Treatment of LM With osimertinb
Other Names:
  • AZD9291
Drug: Bevacizumab
Treatment of LM With osimertinb combined with bevacizumab
Other Names:
  • Anti-VEGF
  • Anti-VEGF Humanized Monoclonal Antibody
  • Anti-VEGF rhuMAb

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intracranial progression-free
Time Frame: Every 6 weeks, up to 2 years,
iPFS (Time from LM diagnosis to the first documentation of intracranial lesion progression or death with documented intracranial pro- gression,)
Every 6 weeks, up to 2 years,
Objective Response Rate
Time Frame: Every 6 weeks, up to 2 years
ORR, proportion of patients with a best overall response of complete response or partial response (CR+PR)
Every 6 weeks, up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
LM Overall survival
Time Frame: Every 3 weeks, up to 5 years,
LM-OS defined as time from LM diagnosis to death due to any cause or last follow-up
Every 3 weeks, up to 5 years,
progression-free survival
Time Frame: Every 6 weeks, up to 2 years,
Proportion of patients progression-free by investigator assessment per RECIST v1.1
Every 6 weeks, up to 2 years,
adverse events
Time Frame: Every 3 weeks, up to 2 years,
Number of patients with adverse events (AEs) as a measure of safety and tolerability
Every 3 weeks, up to 2 years,

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Second Affiliated Hospital of Nanchang University

Collaborators

Nanchang University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

November 1, 2019

Primary Completion (Anticipated)

March 1, 2021

Study Completion (Anticipated)

July 1, 2021

Study Registration Dates

First Submitted

October 3, 2019

First Submitted That Met QC Criteria

November 1, 2019

First Posted (Actual)

November 4, 2019

Study Record Updates

Last Update Posted (Actual)

November 4, 2019

Last Update Submitted That Met QC Criteria

November 1, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • YC2019-S087

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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