Phase II Single Arm Study With CABozantinib in Non-Small Cell Lung Cancer Patients With MET Deregulation
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 25
- 试验地点
- 20
- 主要终点
- Response Rate (RR) (complete + partial responses)
研究概览
简要总结
This is a multicenter, single arm, phase II study evaluating efficacy in terms of RR in a cohort of NSCLC with MET amplification or MET exon 14 skipping mutation pre-treated or not with MET inhibitors.
详细描述
The study population will include NSCLC patients with MET amplification or MET exon 14 skipping mutation pre-treated or not with MET inhibitors. Elegible NSCLC patients with MET exon 14 skipping mutations or MET amplification will be treated with open label orally cabozantinib 60 mg/daily, cycles each 28 days. Disease evaluation will be performed every two months (8 weeks). Patients will be treated with cabozantinib until disease progression, unacceptable toxicity or patient refusal.Treatment will be continued until disease progression, unacceptable toxicity or patient refusal. Treatment beyond disease progression is allowed if considered appropriate by the investigator.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Citological or histological diagnosis of non-small-cell-lung cancer (NSCLC) stage III B (not suitable for local treatments with curative intent) or stage IV.
- •Tissue samples available for MET analysis (archivial tissue or tissue collected at study entry); patients without archival tumor tissue or refusing new biopsy at study entry, are eligible if MET mutation is detected in cf-DNA
- •Presence of MET mutations (exon 14 skipping mutation ONLY) detected in tissue or cf-DNA at the local lab or in the central lab or MET amplification (MET/CEP7 ratio > 2.2) detected in the central lab ONLY.
- •Measurable disease according to RECIST criteria version 1.1
- •At least 1 prior line of standard therapy (chemotherapy and/ or immunotherapy)
- •Performance status 0-1 (ECOG)
- •Age ≥18 years
- •Patients potentially fertile using adequate methods of contraception in order to avoid childbearing. Contraceptive methods must be respected by male and female patients and their partners during study treatment period and at least 4 months after completing therapy
- •Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to enrollment:
- •ANC ≥ 1500 cells/μL without granulocyte colony-stimulating factor support
- •Platelet count ≥ 100,000/μL without transfusion
- •Hemoglobin ≥ 9.0 g/dL Patients may be transfused to meet this criterion
- •AST, ALT, and alkaline phosphatase ≤ 2.5 × ULN, with the following exceptions:
- •Patients with documented liver metastases: AST and/or ALT ≤ 5 × ULN
- •Patients with documented liver or bone metastases: alkaline phosphatase ≤ 5 × ULN.
- •Serum bilirubin ≤ 1.25 × ULN
- •Patients with known Gilbert disease who have serum bilirubin level ≤ 3 × ULN may be enrolled
- •Calculated creatinine clearance (CRCL) ≥ 45 mL/min or calculated CRCL must be ≥ 60 mL/min
- •Patient compliance to the study procedure
- •Written informed consent
排除标准
- •Tissue sample not available in patients without MET exon 14 skipping mutation detected in cf-DNA
- •No possibility to assess MET status
- •Absence of any measurable disease according to RECIST criteria
- •Co-existence of driver events, including EGFR mutations, KRAS mutations, ALK rearrangements or ROS-1 rearrangements
- •No prior therapy
- •Concomitant chemotherapy or immunotherapy or radiotherapy
- •Symptomatic brain metastasis
- •Uncontrolled significant inter-current or recent illness, including cardio-vascular disorders and gastro-intestinal disorders
- •Major surgery within 2 months before first dose of study treatment
- •Concomitant anti-coagulation with oral anti-coagulants or plated inhibitors
- •History of significant bleeding, trachea-bronchial tree/major blood vessels invading tumors, cavity pulmonary lesions and GI disorders associated with a risk of perforation or fistula formation
- •Diagnosis of another cancer in the last 3 years, except for in situ carcinoma of cervix, breast and bladder or skin carcinoma (squamous or basalioid)
- •Pregnancy or breastfeeding
研究组 & 干预措施
Cabozantinib
Elegible NSCLC patients with MET exon 14 skipping mutations or MET amplification will be treated with open label orally cabozantinib 60 mg/daily, cycles each 28 days.
干预措施: Cabozantinib (Drug)
结局指标
主要结局
Response Rate (RR) (complete + partial responses)
时间窗: Up to 36 months
RR will be evaluated by investigators according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Partial and complete responses will be confirmed following RECIST criteria 1.1. Disease evaluation will be performed every two months (8 weeks).
次要结局
- Progression free survival (PFS)(Up to 36 months)
- Disease Control Rate (DCR: stable disease + partial response + complete response)(Up to 36 months)
- Overall survival (OS)(Up to 36 months)
- Exploratory biomarkers(Up to 36 months)