Furmonertinib in Patients With Leptomeningeal Metastases Associated With EGFR Mutated NSCLC

April 3, 2023 updated by: First Affiliated Hospital of Zhejiang University

Efficacy and Safety Analysis of Furmonertinib in Patients With Leptomeningeal Metastases Associated With EGFR Mutated NSCLC，Guiding by Cerebrospinal Fluid ctDNA Detection

The goal of this clinical trial is to evaluate the clinical efficacy and safety of Furmonertinib in EGFR mutated NSCLC patients with leptomeningeal metastasis and to explore the feasibility of CSF ctDNA detection for efficacy evaluation. Participants will be treated with 160mg Furmonertinib daily and tumor evaluation will be performed every 6-8 weeks. The participants' blood and cerebrospinal fluid samples will be collected three times during the study for ctDNA detection.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Enrolling by invitation

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Advanced non-small cell lung cancer patients with leptomeningeal metastases tend to have a worse prognosis. Currently, no standard therapeutic regimen for LM has been established because of its rarity and heterogeneity. Targeted therapy is the primary treatment of patients with EGFRm of NSCLC. The drug concentration in cerebrospinal fluid is the key factors affecting the curative effect of intracranial metastatic lesions. The widespread application of EGFR-TKIs in clinical practice has significantly prolonged the survival period of patients with EGFR mutations, but the standard dose of first- and second-generation EGFR-TKIs show poor control of intracranial metastasis.Furmonertinib is a third-generation EGFR-TKI targeting both sensitising EGFR and EGFR T790M mutations. Phase 2 clinical study of furmonertinib revealed that furmonertinib was clinically effective with acceptable toxicity in patients with EGFR T790M mutated advanced NSCLC, including in patients with CNS metastases. At present, some study has found that the dynamic changes of EGFR in plasma ctDNA can be used to evaluate the prognosis of NSCLC patients. Some study has also observed that the copy number variations in CSF ctDNA of NSCLC patients with LM are related to the curative effect. Therefore, CSF ctDNA may become a new biomarker to assess the therapeutic effect of LM. This is a single-center, open, single-arm, exploratory phase 2 trial evaluating the clinical efficacy and safety of Furmonertinib in EGFR mutated NSCLC patients with leptomeningeal metastasis and to explore the feasibility of CSF ctDNA detection for efficacy evaluation.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Locations

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310003
        • The First Affiliated Hospital, College of Medicine, Zhejiang University

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Provision of signed and dated written informed consent by the patient or legally acceptable representative prior to any study-specific procedures.
  2. Age ≥18 years.
  3. Newly diagnosed NSCLC patients with leptomeningeal metastases associated with EGFR activating mutant or patients who develop leptomeningeal metastases only after treatment with first- or second-generation of EGFR-TKIs.
  4. LM diagnosis was based on the detection of malignant cells in the CSF. Patients with new neurological symptoms and signs or typical MRI findings, together with the EGFR mutations detected by CSF ctDNA, can also be enrolled even if CSF cytology is not positive.
  5. Subjects may be eligible for or have had CNS shunt or Ommaya fluid reservoir implantation. Patients who do not meet the requirements should be able to cooperate with lumbar puncture.
  6. ECOG performance status of 0 to 2.
  7. Life expectancy ≥ 3 months.
  8. Patients must have stable extracranial symptoms and have no CNS complications requiring urgent neurosurgical intervention for at least 4 weeks before study enrollment.
  9. At least one measurable extracranial lesion as defined by RECIST 1.1.
  10. Women of childbearing age (WOCBP) and male subjects should take effective contraception during the treatment and within 3 months after the end of treatment. WOCBP should be non-pregnant within 1 week prior to study enrollment.

Exclusion Criteria:

  1. Previous or current treatment of any third-generation EGFR-TKI.
  2. Previously treated with radiotherapy for central nervous system metastases.
  3. A history of stroke within 6 months or pre-existing central nervous system damage which can interfere with neurological evaluation.
  4. A history of chronic gastrointestinal disease or any other medical condition that would preclude adequate absorption of Furmonertinib.
  5. Currently receiving (or unable to stop use at least 1 week prior to receiving the first dose of Furmonertinib) medications or herbal supplements known to be potent inhibitors or inducers of CYP3A4/5.
  6. A history of previous or current tumors other than NSCLC, with the exception of radical non-melanoma skin cancer, carcinoma in situ of the cervix, benign prostate tumor/hypertrophy, or other cancers that have been radical and have no evidence of relapse for at least 5 years.
  7. Past medical history of any kinds of interstitial lung disease or radiation pneumonitis.
  8. Systemic antitumor therapy with other agents was planned before enrollment or during the duration of the study.
  9. Major surgery procedure or significant traumatic injury within 2 weeks of the first dose of study treatment.
  10. A history of hypersensitivity reactions to the study medicine.
  11. Peripheral neuropathy,greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment.
  12. Any evidence of severe or uncontrolled serosal effusion and systemic diseases, including uncontrolled hypertension, diabetes, cardiovascular disease, active bleeding diatheses and severe acute or chronic infections that require systemic treatment(including positive HbsAg or positive HCV antibodies or confirmed positive HIV test result).
  13. Inadequate bone marrow reserve or organ function.
  14. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Furmonertinib
Furmonertinib 160mg po qd
Drug: Furmonertinib Mesilate Tablets
160mg of Furmonertinib mesilate tablets (given as four 40mg tablets) administered orally once daily
Other Names:
  • AST2818

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Intracranial Progression-Free Survival (PFSi)
Time Frame: Assessed up to 12 months.
PFSi is defined as the time from first dose of Furmonertinib in this study until the date of intracranial disease progression.
Assessed up to 12 months.
Overall Progression-Free Survival (PFSo)
Time Frame: Assessed up to 12 months.
PFSo is defined as the time from first dose of Furmonertinib in this study until the date of disease progression.
Assessed up to 12 months.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: Assessed up to 12 months.
ORR is defined as the percentage of patients with a best response of CR (complete response) or PR (partial response).
Assessed up to 12 months.
Disease Control Rate (DCR)
Time Frame: Assessed up to 12 months.
DCR is defined as the proportion of patients with a best overall, extracranial and CNS, respectively, response of confirmed CR, confirmed PR, or SD.
Assessed up to 12 months.
Overall Survival (OS)
Time Frame: Assessed up to 24 months.
OS is defined as the time from the date of first dose of Furmonertinib in this study until death due to any cause.
Assessed up to 24 months.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Adverse events/Serious adverse events
Time Frame: From signing ICF to 30 days after the end of treatment.
Incidence of Adverse Events (AEs): Incidence, severity and seriousness of adverse events, incidence of serious adverse events (SAEs), which usually be graded by CTCAE v5.0 based on current clinical practice.
From signing ICF to 30 days after the end of treatment.

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
First Affiliated Hospital of Zhejiang University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Yuehong Wang, First affiliated Hospital of Zhejiang University

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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 15, 2022

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2025

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 31, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 3, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 3, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 14, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 14, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 3, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CHNFLM-IIT-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No plan to share participant data of the trial.

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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