A Single-center, Single-arm Phase II Study of Limertinib Plus Carboplatin and Etoposide in EGFR-mutant NSCLC Patients With SCLC Transformation After EGFR-TKI Progression
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
This single-center, prospective study and aims to evaluate the efficacy and safety of limertinib combined with etoposide and carboplatin in EGFR-mutant NSCLC patients who develop small-cell lung cancer transformation following progression on EGFR-TKI therapy.
详细描述
This is a single-center, prospective interventional Phase II study designed to assess the efficacy, safety and mechanism of resistance to limertinib combined with carboplatin and etoposide in EGFR-mutant NSCLC patients who have histologically confirmed small-cell transformation after progression on EGFR-TKI therapy. Thirty patients will receive Limertinib orally once daily (80 mg) plus carboplatin (AUC 5-6, day 1) and etoposide (100 mg/m², days 1-3) every 21 days until disease progression or unacceptable toxicity. Radiographic tumor evaluation will be conducted every 6 weeks per RECIST v1.1. Tumor tissue and blood specimens will be collected at baseline and upon disease progression for next-generation sequencing to elucidate the molecular mechanisms underlying histological transformation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must meet all of the following to be eligible for enrollment:
- •Signed written informed consent prior to any study-related procedures.
- •Age ≥ 18 and ≤ 80 years.
- •Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) with a sensitizing EGFR mutation (exon 19 deletion or L858R, with or without concurrent mutations).
- •Prior treatment with EGFR-TKI, with documented disease progression and histologically confirmed small-cell lung cancer (SCLC) transformation.
- •At least one measurable target lesion per RECIST v1.
- •ECOG performance status 0-1 (see Appendix for ECOG scale).
- •Estimated life expectancy > 3 months.
- •Adequate bone marrow function, defined as:
- •ANC ≥ 1,500/mm³
- •Hemoglobin ≥ 9 g/dL
- •Platelets ≥ 90,000/mm³
- •Adequate hepatic function, defined as:
- •Total bilirubin ≤ 1.5 × ULN
- •AST and ALT ≤ 2.5 × ULN (or ≤ 5 × ULN in patients with known hepatic metastases)
- •Adequate renal function, defined as:
- •Serum creatinine within normal limits OR creatinine clearance ≥ 50 mL/min (Cockcroft-Gault)
- •For patients with BMI < 18.5 or > 30, eGFR ≥ 50 mL/min (MDRD) is acceptable
- •Adequate cardiac function, defined as LVEF ≥ 50% by MUGA scan or echocardiography.
- •Women of childbearing potential and men with partners of childbearing potential must agree to use effective contraception.
排除标准
- •Patients meeting any of the following criteria will be excluded from the study:
- •Histology at initial diagnosis of small-cell lung cancer (SCLC), large-cell carcinoma, or mixed tumor with predominant SCLC, large-cell, or neuroendocrine components.
- •Prior treatment with a standard SCLC chemotherapy regimen (e.g., carboplatin/etoposide or cisplatin/etoposide) after SCLC transformation.
- •Symptomatic or unstable brain metastases. Patients with a history of unstable brain metastases must have undergone definitive surgery or radiotherapy, remain clinically stable, and be off corticosteroids for cerebral edema for at least 14 days before enrollment.
- •Any concurrent malignancy other than basal cell carcinoma of the skin or carcinoma in situ of the cervix. (Patients with a prior malignancy must be disease-free for ≥ 5 years to be eligible.)
- •Pregnancy (confirmed by serum ß-hCG) or breastfeeding. Note: Women who have been postmenopausal for ≥ 12 months, or who have undergone hysterectomy, bilateral oophorectomy, or bilateral tubal ligation, are exempt from contraception requirements. Male participants must use effective contraception from the first dose of study drug until 180 days after the last dose.
- •Active hepatitis B (HBV DNA > 1,000 IU/mL) or hepatitis C infection (anti-HCV positive and/or HCV RNA > 15 IU/L), or known HIV infection.
- •Known hypersensitivity to lietinib, carboplatin, or etoposide.
- •Psychiatric or cognitive disorders that would preclude informed consent or compliance with study requirements.
- •Women planning pregnancy during the screening period or who, along with their partners, are not using effective contraception.
- •Any other medical or psychosocial condition judged by the investigator to compromise patient safety or study integrity (e.g., poor compliance or comorbidities affecting efficacy assessment).
研究组 & 干预措施
Experimental group
Limertinib Carboplatin Etoposide
干预措施: limertinib (Drug)
Experimental group
Limertinib Carboplatin Etoposide
干预措施: etoposide and carboplatin (Drug)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: Time from first subject dose to study completion, or up to 36 month
define as first dose to first documented disease progression assessed by investigator or death due to any cause
次要结局
- Duration of Response (DoR)(Time from first subject dose to study completion, or up to 36 month)
- Adverse events (AEs)(From first dose to the last dose, up to 24 month)
- Objective Response Rate (ORR)(Time from first subject dose to study completion, or up to 36 month)
- Disease control response (DcR)(Time from first subject dose to study completion, or up to 36 month)
研究者
Yongchang Zhang
Director, Head of Medical Oncology, Principal Investigator, Clinical Professor
Hunan Province Tumor Hospital