Crizotinib in Pretreated Metastatic Non-small-cell Lung Cancer With MET Amplification or MET Exon 14 Mutation or ROS1 Translocation (METROS)
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 80
- 试验地点
- 26
- 主要终点
- Response rate to crizotinib in patients with ROS1 translocation or MET amplification or MET exon 14 mutation
研究概览
简要总结
Phase II, two arms, parallel, non comparative study with crizotinib in patients with ROS 1 translocation or MET amplification or MET exon 14 mutation
详细描述
This is a phase II, prospective, two arms, parallel, non comparative study with crizotinib in pretreated NSCLC patients with ROS1 translocation or MET amplification or MET exon 14 mutation (figure 1). Patients with locally advanced or metastatic NSCLC, pretreated with at least one previous chemotherapy line and with at least one measurable tumor lesion will be considered eligible for the trial. All potentially eligible patients will be evaluated for MET and ROS1 by FISH to detect MET amplification or ROS1 translocation. MET mutation will be assessed using direct sequencing or high sensitive methods. After evaluation of inclusion and exclusion criteria, and after signature of informed consent form, all MET amplified or MET exon 14 mutation or ROS1 translocated eligible patients will receive crizotinib 250 mg BID p.o until disease progression, unacceptable toxicity or patient refusal.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of NSCLC
- •Availability of tumor tissue for ROS1 and MET analyses
- •Patient positive for ROS1 translocation or MET amplification
- •At least one radiological measurable disease according to RECIST criteria (Response Evaluation Criteria in Solid Tumors )
- •At least 1 previous standard chemotherapy regimen
- •Performance status 0-2 (ECOG)
- •Patient compliance to trial procedures
- •age ≥ 18 years
- •Written informed consent
- •Adequate BM function (ANC ≥ 1.5x109/L, Platelets ≥ 100x109/L, HgB > 9g/dl)
- •Adequate liver function (bilirubin <G2, transaminases no more than 3xULN/<5xULN in present of liver metastases).
- •Normal level of alkaline phosphatase and creatinine.
- •If female: childbearing potential either terminated by surgery, radiation, or menopause, or attenuated by use of approved contraceptive method [intrauterine contraceptive device (IUD), birth control pills, or barrier device] during and for ninety(90) days after end of treatment.
排除标准
- •No tumor tissue available or patient negative for ROS1 translocation or MET amplification
- •Absence of any measurable lesion
- •For ROS1+ patients: Previous therapy with crizotinib or any anti-ALK agent
- •For MET amplified patients: Evidence of MET amplification in tumor tissue collected in EGFR mutant patient at time of EGFR-TKI acquired resistance occurrence. An EGFR mutant patient is eligible if MET amplification is detected in a tumor specimen collected before starting an EGFR-TKI
- •No previous chemotherapy
- •Concomitant radiotherapy or chemotherapy.
- •Previous radiotherapy on the target lesion(s). If all sites were included in radiotherapy fields patient is eligible only if there is evidence of progressive disease after completion of radiotherapy.
- •Symptomatic brain metastases
- •Diagnosis of any other malignancy during the last 5 years, except for in situ carcinoma of cervix uteri and squamous cell carcinoma of the skin
- •Pregnancy or lactating
- •Other serious illness or medical condition potentially interfering with the study
研究组 & 干预措施
Patients with MET amplification or MET exon 14 mutation
Pretreated NSCLC patients with MET amplification or MET exon 14 mutation with locally advanced or metastatic NSCLC and with at least one measurable tumor lesion will be considered eligible for the trial and they will receive crizotinib 250 mg BID p.o until disease progression, unacceptable toxicity or patient refusal.
干预措施: Crizotinib (Drug)
Patients with ROS1 translocation
Pretreated NSCLC patients with ROS1 translocation with locally advanced or metastatic NSCLC and with at least one measurable tumor lesion will be considered eligible for the trial and they will receive crizotinib 250 mg BID p.o until disease progression, unacceptable toxicity or patient refusal.
干预措施: Crizotinib (Drug)
结局指标
主要结局
Response rate to crizotinib in patients with ROS1 translocation or MET amplification or MET exon 14 mutation
时间窗: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 100 months
次要结局
- Progression-free survival (PFS)(From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 100 months)
- Overall Survival (OS)(From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 100 months)
- Toxicity analysis: Incidence of Grade 3-4 Grade Toxicity graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0(From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 100 months)
- Correlation with additional tumor biomarkers in tumor tissue or blood(From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 100 months)
- Response according to different levels of ROS1 translocation or MET amplification (ratio >2.2 and <5 versus ratio ≥ 5) or MET exon 14 mutation(From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 100 months)