A Single Arm, Open-label, Phase 2 Study to Assess the Efficacy and Safety of Lucitanib Given Orally as a Single Agent to Patients With Advanced/Metastatic Lung Cancer and FGF, VEGF, or PDGF Related Genetic Alterations
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 18
- 试验地点
- 19
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
The purpose of this study is to determine whether lucitanib is safe and effective in the treatment of patients with advanced/metastatic lung cancer and fibroblast growth factor (FGF), vascular endothelial growth factor receptor (VEGF), or platelet derived growth factor (PDGF) related genetic alterations.
详细描述
Lucitanib is an oral inhibitor of the tyrosine kinase activity of FGFR 1-3, VEGFR 1-3, and PDGFR α/β. Lucitanib has demonstrated potent anti-tumor and anti-angiogenic activity in vitro proliferation assays and in vivo using human tumor xenograft models, with a trend for stronger efficacy in those with genomic aberrancies of FGF or PDGF. Abnormalities in the FGF, VEGF, and PDGF-related genes are observed across lung cancer histologies.
The first in human trial of lucitanib demonstrated that daily lucitanib is clinically active in patients with advanced solid tumors. Specifically, patients with FGFR1-amplification appeared to derive particular benefit from lucitanib.
Based on these results, this study is designed to explore the safety and anti-tumor activity of daily lucitanib in lung cancer patients with FGF, VEGF, and PDGF genetic alterations.
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
- •Histologically or cytologically confirmed advanced/metastatic SCLC or NSCLC
- •Any of the following tumor tissue based genetic alterations: FGFR1, FGFR2, FGFR3, VEGFA, or PDGFRα amplification; Any FGFR1, FGFR2, or FGFR3 gene fusion; FGFR1, FGFR2, or FGFR3 activating mutation
- •Availability of tumor tissue sample suitable for the central confirmation of the genetic alteration and exploratory analyses
- •Eastern Cooperative Oncology Group (ECOG) of 0 or 1
- •Measurable disease per RECIST 1.1
- •Documented radiographic disease progression following at least one line of therapy in the advanced/metastatic setting
排除标准
- •Tumors that are invading a major vessel; NSCLC tumors abutting to a major vessel
- •Uncontrolled hypertension, defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg with optimized anti-hypertensive therapy
- •Uncontrolled hypothyroidism defined as serum thyroid stimulating hormone (TSH) higher than 5 mIU/mL while receiving appropriate thyroid hormone therapy
- •Symptomatic and/or untreated central nervous system metastases
- •Presence of another active cancer
- •Ongoing adverse events from surgery or prior anti-cancer therapies, including radiation, targeted, or cytotoxic therapies
- •Pregnant or breastfeeding women
研究组 & 干预措施
Lucitanib
Lucitanib given orally once daily on a continuous schedule. Starting dose is 10 mg/day.
干预措施: Lucitanib (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Screening, every 8 weeks; up to 2 years
Proportion of patients in whom a confirmed Complete Response (CR) or a confirmed Partial Response (PR), as best overall response according to RECIST criteria, is observed.
次要结局
- Progression-Free Survival (PFS)(Screening, every 8 weeks; up to 2 years)
- Clinical Benefit Rate (CBR)(Screening, every 8 weeks; up to 2 years)
- Tumor growth kinetics(Screening, every 8 weeks; up to 2 years)
- Incidence of adverse events (AEs), clinical laboratory abnormalities, and dose modifications(Continuously; up to 2 years)
- PK parameters of lucitanib(Cycle 1 Day 14 and 28, Cycle 2 Day 28, Cycle 3 Day 28)
- Duration of response (DOR)(Screening, every 8 weeks; up to 2 years)
- Duration of clinical benefit(Screening, every 8 weeks; up to 2 years)
- Overall Survival (OS)(Continuously; up to 2 years)
- Pharmacogenomic analysis of inter-patients variation in gene encoding ADME involved proteins(Cycle 1 Day 1)
- Pharmacodynamic (PD) evaluation of lucitanib profile(Cycle 1 Day 1 and 14, End of Study)