Open-label, Single-Arm, Multicenter Clinical Study of EGFR-TKIs Sequentially Combined With Bevacizumab for the Treatment of EGFR-Mutant Advanced Non-Small Cell Lung Cancer, Based on Early Warning by CSF CTC Capture Technology
Overview
- Phase
- Early Phase 1
- Intervention
- Osimertinib 80 MG
- Conditions
- Non Small Cell Lung Cancer
- Sponsor
- Second Affiliated Hospital of Nanchang University
- Enrollment
- 100
- Primary Endpoint
- Overall Survival（OS）
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •1.The subjects voluntarily joined this study and signed the informed consent form, showing good compliance and cooperation with follow-up.
- •2.Ages between 18 years old (inclusive) and 75 years old (inclusive). 3.ECOG score: 0-2 points. 4.Expected survival of no less than 3 months. 5.According to the RECIST 1.1 criteria, the patient has at least one extracranial target lesion.
- •6.Diagnosed with non-small cell lung cancer based on histology or cytology. 7.No leptomeningeal metastasis (EANO criteria). 8.The tumor tissue samples or blood samples are confirmed to have EGFR-sensitive mutations (including exon 19 deletions or L858R).
- •9.Have not received systemic anti-tumor treatment, and are planned to receive first-line monotherapy with osimertinib, aumolertinib, or furmonertinib.
- •10.The main organ functions are normal, that is, they meet the following criteria:
- •The standard for routine blood test should meet: HB≥90 g/L; ANC≥1.5×10\^9/L; PLT≥80×10\^9/L.
- •The biochemical examination should meet the following standards: TBIL\<1.5×ULN; ALT and AST\<2.5×ULN; serum Cr≤1.25×ULN or endogenous creatinine clearance \> 45 ml/min (Cockcroft-Gault formula). 11.Women of childbearing age must have taken reliable contraceptive measures and have undergone a pregnancy test (serum or urine) within 7 days before enrollment, with a negative result, and must be willing to use appropriate methods of contraception during the trial period and for 8 weeks after the last administration of the trial medication. For men, they must agree to use appropriate methods of contraception during the trial period and for 8 weeks after the last administration of the trial medication or have undergone surgical sterilization.
Exclusion Criteria
- •Subjects have received any of the following treatments:
- •Previously used any EGFR tyrosine kinase inhibitors;
- •Previously received any chemotherapy for lung cancer;
- •Previously received any radiotherapy for lung cancer (except for palliative radiotherapy for bone metastases);
- •Within 4 weeks before the first administration of the study medication, the subject had undergone major surgery;
- •Within 7 days before the first administration of the study medication, used strong inhibitors or inducers of CYP3A
- •Subjects with concurrent other malignant tumors, except for basal cell carcinoma of the skin and in situ cancer.
- •Subjects have uncontrollable malignant pleural effusion and pericardial effusion.
- •Subjects who are allergic to contrast agents used in CT and MRI or who cannot tolerate MRI examinations.
- •As judged by the investigator, there are any serious or poorly controlled systemic diseases, such as poorly controlled hypertension, active bleeding diathesis, or active infection.
Arms & Interventions
Sequential Treatment cohort
Participants receive osimertinib orally at a dose of 80mg daily for a 28-day treatment period. After the start of treatment, cerebrospinal fluid is collected every 12 weeks for circulating tumor cell (CTC) examination and routine cytopathological assessment. If the routine cytopathological test is positive, participants are sequentially treated with continued osimertinib at 80mg daily, in combination 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. A continuous treatment of 21 days constitutes one treatment cycle. After the initiation of treatment, cerebrospinal fluid is collected every 6 weeks for CTC testing and routine cytopathological examination.
Intervention: Osimertinib 80 MG
Sequential Treatment cohort
Participants receive osimertinib orally at a dose of 80mg daily for a 28-day treatment period. After the start of treatment, cerebrospinal fluid is collected every 12 weeks for circulating tumor cell (CTC) examination and routine cytopathological assessment. If the routine cytopathological test is positive, participants are sequentially treated with continued osimertinib at 80mg daily, in combination 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. A continuous treatment of 21 days constitutes one treatment cycle. After the initiation of treatment, cerebrospinal fluid is collected every 6 weeks for CTC testing and routine cytopathological examination.
Intervention: Bevacizumab
Outcomes
Primary Outcomes
Overall Survival（OS）
Time Frame: From the start of therapy until death due to any cause, assessed up to 2 years after completion of treatment
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.
Secondary Outcomes
- Objective response rate (ORR)(Within 8 weeks after completion of treatment)
- Progression free survival (PFS)(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)(Up to 2 years after completion of treatment)