A Phase II, Single-Center, Single-Arm, Prospective Study of Neoadjuvant Lazertinib Therapy in Resectable EGFR-Mutation Positive Lung Adenocarcinoma Patients Detected by Broncho-alveolar Lavage Fluid(BALF) Liquid Biopsy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Objective response rate
研究概览
简要总结
Complete surgical resection is the standard treatment in early-stage lung cancer. However, the patients with early resected Epidermal Growth Factor Receptor(EGFR)-mutated lung cancers have high recurrence rate. The efficacy of neoadjuvant treatment by first-generation EGFR-Tyrosine Kinase Inhibitor(TKI) has been demonstrated, however, that of the third-generation EGFR-TKI(lazertinib) has not yet been fully investigated. The aim of this study is to evaluate the efficacy of neoadjuvant Lazertinib in resectable EGFR mutation-positive NSCLC and clinical application of extracellular vesicles(EVs) based BALF liquid biopsy to identify EGFR mutation without invasive tissue biopsy.
详细描述
The neoadjuvant treatment of 3rd-generation EGFR-TKI, lazertinib for 9 weeks before surgery is administrated. After the surgery, the patients with the tumor over stage 2 are given the lazertinib to prevent recurrence for 3 years or until recurrence. In early lung cancer, a tissue biopsy is often difficult due to the small size or the risky location. We collect bronchoalveolar lavage fluid for liquid biopsy and lazertinib is administrated according to the result of BALF liquid EGFR genotyping.
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
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 19 years
- •Patients with suspected lung cancer on chest CT findings
- •Patients with the following EGFR gene mutations in the test on bronchoalveolar lavage fluid: E19Del, L858R alone or concurrent rare EGFR gene mutations (T790M, G719X, exon 20 insertion, S768I)
- •Patients whose tumor can be completely resected by surgery: patients with stage I-IIIB, or stage IVA who has single metastasis
- •Patients not previously treated with EGFR-TKIs such as gefitinib, erlotinib, afatinib, dacomitinib
- •Patients with the measurable lesion of 1 cm or more according to RECIST v1.1
- •Eastern Cooperative Oncology Group (ECOG) 0-1
- •EGFR-TKIs (gefitinib, erlotinib, afatinib,dacomitinib) naive patients
- •Patients with adequate pulmonary and heart function for surgery
- •Adequate organ function defined as Hemoglobin ≥ 9.0g/dL Absolute neutrophil count ≥ 1500/mm3 Platelet ≥ 100,000 /mm3 Serum creatinine≤ normal range*1.5x Aminotransferase/Alkaline phosphatase ≤normal range*2.5x Total bilirubin ≤1.5 mg/dL Liver metastasis: Aminotransferase/Alkaline phosphatase ≤ normal range* 5x Bone metastasis Alkaline phosphatase ≤ normal range* 5x
- •Female patients with childbearing potential should be using adequate contraceptive measures. Female patients must have evidence of non-child-bearing potential(Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments)
- •Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception for at least 14 days prior to administration of the first dose of study treatment, during the study, and for 3 months following the last dose of Lazertinib.
排除标准
- •Uncontrolled active interstitial lung disease
- •Pathologically confirmed N3 disease
- •Uncontrolled stage III-IV other malignancy
- •Uncontrolled Hypertension, Congestive Heart failure with New York Heart Association(NYHA) ≥ 3, acute myocardial infarct history within 6 months before screening. 2nd- 3rd Atrio-Ventricular(AV) block or complete AV block
- •Gastrointestinal diseases (e.g. Chron's disease, ulcerative colitis) or malabsorption syndrome that would impact on drug absorption
- •Active infection requiring ongoing treatment(e.g. active Hepatitis B virus, Hepatitis C virus or Human immunodeficiency virus)
- •History of hypersensitivity to active or inactive excipients of Lazertinib or drugs with a similar chemical structure.
- •No ability to comply with protocol requirements.
研究组 & 干预措施
Neoadjuvant Lazertinib
Lazertinib as neoadjuvant treatment is administrated for 9 weeks before surgery. After surgical intervention the treatment is administrated upto 3 years to the patients with over stage 2 tumor. Treatment is discontinued in case of unacceptable toxicity or disease progression.
干预措施: Neoadjuvant lazertinib (Drug)
结局指标
主要结局
Objective response rate
时间窗: 9 weeks after the starting day of the lazertinib
The objective response rate (ORR) evaluated with RECIST version 1.1. It is defined as the proportion of patients with complete response (CR) or partial response (PR) after 9 weeks of lazertinib administration
次要结局
- Down-staging rate(From the day of screening to an average of 16 weeks after the first dose)
- Major pathological response(From the day of screening to an average of 16 weeks after the first dose)
- The concordance rate of EGFR mutations between surgical tissue and BAL fluid samples(From the day of screening day to an average of 16 weeks after the first dose)
- Disease-free survival rate(up to 3 years after surgery)
研究者
Kye Young Lee
Professor
Konkuk University Medical Center