Phase I Dose-escalation Trial of Simmitinib for Patients With Advanced Solid Tumors in Therapeutic Failure
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Dose-limited toxicity (DLT)
研究概览
简要总结
This is an open label, multi-center, phase I study of oral Simmitinib in subjects with advanced solid tumors including gastric cancer.
详细描述
This is an open label, multi-center, phase I study of oral Simmitinib in subjects with advanced solid tumors including gastric cancer [including gastroesophageal cancer], cholangiocarcinoma, lung squamous cell carcinoma, urothelial transitional cell carcinoma, and estrogen-receptor-positive breast cancer patients [ER+], etc. This phase I study will evaluate the safety, tolerability, pharmacokinetics and the preliminary efficacy of the FGFR/KDR/CSF1R multi-target inhibitor Simmitinib.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary written informed consent of the patient obtained before any study-specific procedure；
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1;
- •Patients with histologically/cytologically confirmed diagnosis of advanced solid tumors refractory to standard therapy or for whom no standard therapy exist;
- •Adequate washing period from last anti-tumor therapy;
- •Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1;
- •The expected survival time for more than 12 weeks;
- •Adequate bone marrow, hepatic, renal, pancreas, and coagulation function, Blood phosphorus and calcium in the normal range.
排除标准
- •Prior treatment with selective FGFR inhibitors or multi-target kinase Inhibitors with FGFR as the main target;
- •Unrecovered from any drug-related adverse event to grade ≤ 1 according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.3.0 derived from any previous anti-tumor treatment, excluding alopecia, Pigmentation, or other toxicity with little safety risk for subjects;
- •Active Central Nervous System (CNS) metastases (brain or leptomeningeal metastases, etc.);
- •Any other history of malignancy within 3 years;
- •Congenital coagulation abnormalities. Active bleeding or previous history of massive bleeding (>30ml within 3 months), history of hemoptysis (more than 5ml fresh bleeding within 4 weeks);
- •Corneal diseases of clinical significance. There is a history of retinal pigment epithelial detachment or evidence of the presence of retinal pigment epithelial detachment. History of age-related macular degeneration or evidence of age-related macular degeneration exists；
- •Subjects with impaired cardiac function or heart disease of clinical significance;
- •Pregnant or lactating women.
研究组 & 干预措施
Simmitinib tablet
The core trial period includes 4-weeks Screening stage (28d), 7-days single administration stage, 4-weeks multiple administration stage (28d), 3-days blood collection stage of PK after multiple administration.
The starting dose was set at 1mg/d on toxicology data. Dosing will continue uninterrupted for 28 days in multiple administration stage.
The dose-limiting toxicity (DLT) period assessment will be from the first administration of Simmitinib tablet to the end of the first cycle (35 days).
干预措施: Simmitinib (Drug)
结局指标
主要结局
Dose-limited toxicity (DLT)
时间窗: 1 year
To identify the dose-limited toxicity (DLT).
Maximum tolerated dose (MTD)
时间窗: 1 year
To identify the maximum tolerated dose (MTD).
Recommended Phase II Dose (RP2D)
时间窗: 1 year
To identify the Recommended Phase II Dose (RP2D).
次要结局
- Median overall survival (OS)(2 year)
- Time of peak plasma concentration (Tmax)(2 year)
- Median progression free survival (PFS)(2 year)
- Peak Plasma Concentration (Cmax)(2 year)
- Overall response rate (ORR)(2 year)
- Area under the plasma concentration versus time curve (AUC)(2 year)
- Duration of Response (DoR)(2 year)
- Gene status(2 year)