clinical trial The goal of this clinical trial is to learn whether the treatment of advanced non-small cell lung cancer with EGFR-TKIs, when combined with bevacizumab in the presence of positive circulating tumor cells in the cerebrospinal fluid, has better therapeutic efficacy. The main questions it aims to answer are:1.When EGFR-TKIs are sequentially combined with bevacizumab along with EGFR-TKIs for first-line treatment of advanced non-small cell lung cancer, how long can the participants survive? 2.What medical problems do participants have when using EGFR-TKIs sequentially combined with bevacizumab in conjunction with EGFR-TKIs. Participants will: Receive EGFR-TKIs treatment for a duration of 3 months, and upon a positive cerebrospinal fluid tumor cell status, subsequently receive bevacizumab combined with EGFR-TKIs treatment until disease progression. Visit the clinic for check-ups and tests every two weeks, and have follow-up visits every six weeks after the treatment ends. Keep a record of their symptoms and disease progression.
This study is an open-label, single-arm, multicenter, exploratory clinical trial designed to evaluate and observe the first-line treatment of locally advanced/advanced non-small cell lung cancer that is positive for EGFR mutations, based on the early warning of a novel cerebrospinal fluid CTC capture technology. Subjects who meet all inclusion criteria and none of the exclusion criteria will first receive EGFR-TKIs (osimertinib, amivantamab, or futibatinib) treatment (as per the instruction manual). After a positive cerebrospinal fluid tumor cell status, they will then sequentially receive bevacizumab (7.5mg/kg, intravenous injection, once every 3 weeks) combined with EGFR-TKIs treatment. Participants Aged 18 years or older (including 18 years old) and up to 75 years of age (including 75 years old); confirmed non-small cell lung cancer through histology or cytology; confirmed EGFR sensitive mutation (exon 19 deletion or L858R) prior to treatment; planned to receive first-line monotherapy with EGFR-TKIs (osimertinib, amivantamab, or futibatinib). This study is an open-label, single-arm, multicenter, exploratory clinical trial. The primary research objective is to evaluate the overall survival time (OS) of patients with locally advanced/advanced EGFR-mutant non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs) sequentially combined with bevacizumab as a first-line treatment, based on the early warning of a novel cerebrospinal fluid circulating tumor cell (CSF CTC) capture technology. The study endpoint is the overall survival time (OS) of the patients. Referring to the results of our team's prospective study data and historical literature review study data, it is anticipated that the hazard ratio (HR) for overall survival (OS) of EGFR-TKIs sequentially combined with bevacizumab compared to EGFR-TKIs as a first-line treatment for high-risk patients with EGFR-mutant locally advanced/advanced NSCLC and leptomeningeal metastasis will be 0.78 (median OS improved from 18 months to 21 months). After the first subject is enrolled, with the longest observation period being 24 months, α set at two-sided 0.05, and a power of 80%, calculating with a 25% CSF tumor cell positivity rate and a 10% loss to follow-up rate, using the NCSS\&PASS 15.0 software and the single-sample Logrank test method, after sample correction, this study plans to enroll approximately 100 subjects. Based on the investigator-assessed Overall Survival (OS) as the primary efficacy endpoint, the median survival time will be estimated using the Kaplan-Meier method, and the median event time along with its two-sided 95% confidence interval will be presented. Additionally, the hazard ratio and its 95% confidence interval will be estimated as the main analysis.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
100
Osimertinib is taken orally at a dose of 80mg daily for a 28-day treatment period, followed by a sequential treatment of osimertinib 80mg daily taken orally for another 28 days.
Sequential combination therapy with bevacizumab administered intravenously at a dosage of 7.5mg/kg of body weight on the first day of each cycle, with medication given once every 3 weeks, for a continuous treatment duration of 21 days.
Overall Survival(OS)
From the time of a patient's diagnosis or the commencement of treatment, to the time of the patient's death.Will be estimated using Kaplan-Meier product-limit method. The median OS times with two-sided 95% CIs will be estimated.
Time frame: From the start of therapy until death due to any cause, assessed up to 2 years after completion of treatment
Objective response rate (ORR)
Defined as the percentage of participants having an objective response (complete response \[CR\] or partial response \[PR\]), according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. The ORR of the drug will be assessed according to Simon's two stage design. The estimated ORR will be compared to the response rate specified in the null hypothesis (6%) using one-sided exact binomial test at type I error 5%. 95% confidence interval (C.I.) will be also reported.
Time frame: Within 8 weeks after completion of treatment
Progression free survival (PFS)
Will be determined by the immune complete response (iCR). Will be estimated using Kaplan-Meier product-limit method. The median PFS times with two-sided 95% CIs will be estimated.
Time frame: From the start of therapy until disease progression, or death due to any cause, assessed up to 2 years after completion of treatment
Duration of Response (DOR)
Defined as the time from an initial objective response (CR or PR) according to RECIST v 1.1 until disease progression, or death due to any cause, as determined by iCR.
Time frame: Up to 2 years after completion of treatment
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