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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04148898
Recruitment Status : Not yet recruiting
First Posted : November 4, 2019
Last Update Posted : November 4, 2019
Sponsor:
Collaborator:
Nanchang University
Information provided by (Responsible Party):
Second Affiliated Hospital of Nanchang University

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Leptomeningeal Metastasis Non-small Cell Lung Cancer EGFR Activating Mutation Drug: Osimertinib Drug: Bevacizumab Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Crossover Assignment
Masking: Single (Outcomes Assessor)
Masking Description: single
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Osimertinib Alone or in Combination With Bevacizumab for EGFR- Mutant Non-small Cell Lung Cancer With Leptomeningeal Metastasis
Estimated Study Start Date : November 1, 2019
Estimated Primary Completion Date : March 1, 2021
Estimated Study Completion Date : July 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: osimertinb group
Osimertinib 80 mg oral daily
Drug: Osimertinib
Treatment of LM With osimertinb
Other Name: 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 Name: AZD9291

Drug: Bevacizumab
Treatment of LM With osimertinb combined with bevacizumab
Other Names:
  • Anti-VEGF
  • Anti-VEGF Humanized Monoclonal Antibody
  • Anti-VEGF rhuMAb




Primary Outcome Measures :
  1. 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,)

  2. 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)


Secondary Outcome Measures :
  1. 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

  2. progression-free survival [ Time Frame: Every 6 weeks, up to 2 years, ]
    Proportion of patients progression-free by investigator assessment per RECIST v1.1

  3. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04148898


Contacts
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Contact: Liu Anwen, Phd +8613767120022 awliu666@163.com
Contact: Cai Jing, Phd +8615270905381 cjdl879@163.com

Sponsors and Collaborators
Second Affiliated Hospital of Nanchang University
Nanchang University
Investigators
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Study Director: Liu Anwen, Phd Second Affiliated Hospital of Nanchang University

Publications:

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Responsible Party: Second Affiliated Hospital of Nanchang University
ClinicalTrials.gov Identifier: NCT04148898    
Other Study ID Numbers: YC2019-S087
First Posted: November 4, 2019    Key Record Dates
Last Update Posted: November 4, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Second Affiliated Hospital of Nanchang University:
leptomeningeal metastasis
non small cell lung cancer
EGFR Activating Mutation
Osimertinib
Bevacizumab
Additional relevant MeSH terms:
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Lung Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Bronchial Neoplasms
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Carcinoma, Non-Small-Cell Lung
Meningeal Carcinomatosis
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Neoplastic Processes
Pathologic Processes
Nervous System Diseases
Bevacizumab
Osimertinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors