Induction Lorlatinib for ALK Fusion Locally Advanced Non-small Cell Lung Cancer: A Prospective, Single Arm, Open-label Phase 2 Study
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 48
- 试验地点
- 4
- 主要终点
- Pathological Complete Response (pCR)
研究概览
简要总结
A prospective, single-arm, open-label phase 2 study that evaluates the efficacy and safety of induction Lorlatinib in stage III non-small cell lung cancer and explores the clinical feasibility of dynamic ctDNA and multidisciplinary assessment in guiding local treatments.
详细描述
Simon two-stage was applied to estimate the required sample size for the study. Overall an estimated 43 patients were required and at least 12 patients achieved pathological complete response would be deemed as positive result. Patients will be provided 3 cycles induction Lorlatinib 100mg and then assessed whether patients would be eligible for radical surgery or local radiotherapy through multidisciplinary evaluation. After local intervention, patients could choose consolidation treatment of Lorlatinib for up to 2 years or adjuvant doublet chemotherapy for up to 4 cycles. Dynamic blood samples will be collected before and after induction Lorlatinib as well as consolidation treatment. The primary endpoints is pCR for patients who received radical surgery.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age :18 Years to 75 Years;
- •ECOG physical score 0-2 points; expected survival time ≥ 1 year;
- •Pathologically confirmed diagnosis with Stage III NSCLC which harbored ALK fusion detected by next generation sequencing (NGS) or immunohistochemistry (IHC) with or without FISH. Suspected N2 (station 2/4/7) for stage III disease should be confirmed by either mediastinoscopy or EBUS.
- •At least one measurable target lesion according to the RECIST 1.1 standard;
- •The main organ function meets the following criteria: 1) blood routine: absolute value of neutrophils ≥ 1.5 × 109 / L, platelets ≥ 75 × 109 / L, hemoglobin ≥ 80 g / L; 2) blood biochemistry: total bilirubin ≤ 1.5 times the upper limit of normal value, aspartate aminotransferase and alanine aminotransferase ≤ 2.5 times the upper limit of normal value (if liver metastasis, ≤ upper limit of normal value 5 times), serum creatinine ≤ 1.5 times the upper limit of normal;
- •Subjects voluntarily joined the study and signed informed consent, with good compliance to follow-up.
排除标准
- •Stage I, stage II and metastatic stage IV NSCLC;
- •Histologically confirmed small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer);
- •Patients who have previously used any other anti-tumor drugs or received surgery/radiotherapy;
- •Patients with any underlying disease that investigators consider it may affect patient's prognosis including sever cardiovascular, pulmonary disease or serious infections.
- •Clinically obvious gastrointestinal abnormalities, which may affect the intake, transport or absorption of drugs (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.), or patients with total gastrectomy;
- •Pregnant or lactating women; those who have fertility are unwilling or unable to take effective contraceptive measures;
- •Patients with low compliance or willingness to take the drugs and surveillance.
研究组 & 干预措施
Treatment Arm
Patients will receive 12-week induction Lorlatinib followed by radical surgery or local radiotherapy or continue Lorlatinib through MDT and optional consolidation lorlatinib for up to 2 years.
干预措施: Lorlatinib (Drug)
结局指标
主要结局
Pathological Complete Response (pCR)
时间窗: After surgery (approximately 2 weeks)
The pathological complete response is defined as the absence of residual tumor in both lung and regional lymph nodes after induction treatment and radical surgery.
次要结局
- Event-free Survival (EFS)(From date of radical surgery till the date of first documented disease relapse, assessed up to 48 months)
- Dynamic ctDNA alteration(From induction treatment till completion of consolidation lorlatinib (approximately 2.5 years))
- Overall Survival (OS)(From date of induction treatment till the date of death from any cause, assessed up to 60 months.)
- Adverse Events (AEs)(From Initiation of induction treatment till treatment discontinuation, assessed up to 24 months.)
- Progression-free Survival (PFS)(From date of induction treatment till the date of first documented disease progression or death, whichever came first, assessed up to 48 months)
- Objective Response Rate (ORR)(After last dose of induction treatment (approximately 1 week))
研究者
Wen-zhao ZHONG
Head of Pulmonary Surgery
Guangdong Provincial People's Hospital