A Phase II Clinical Study of Trifluridine/Tipiracil Combined With Anlotinib as Second-line Treatment for Recurrent and Metastatic Esophageal Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
Esophageal squamous cell carcinoma (ESCC) is one of the malignant tumors with a high incidence worldwide, especially remaining persistently high in Asian regions. Despite advancements in early diagnosis and comprehensive treatment, most patients are already in the locally advanced or metastatic stage at the time of initial diagnosis, resulting in an extremely poor prognosis. The objective response rate (ORR) of first-line chemotherapy regimens (such as platinum-containing dual-drug combinations with fluorouracil) is less than 50%, and the median progression-free survival (PFS) is only 3-6 months. Moreover, the options for second-line treatment are more limited. Currently, there is no unified standard for second-line treatment, and there is an urgent need to explore new and effective regimens.
Anlotinib is a multi-target tyrosine kinase inhibitor that can target and inhibit vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), and platelet-derived growth factor receptor (PDGFR). It exerts anti-tumor effects through anti-angiogenesis and regulation of the tumor microenvironment. Single-agent anlotinib has shown certain efficacy in advanced esophageal cancer. A phase II study indicated that the ORR of single-agent anlotinib in second-line treatment was 9.7%, with a median PFS of 3.0 months.
Suyuan (trifluridine/tipiracil) is a new oral fluoropyrimidine drug composed of trifluridine (a cytotoxic component) and tipiracil (a synergist that inhibits the metabolic enzyme TP), which can overcome the resistance to traditional fluorouracil. Single-agent Suyuan has achieved significant survival benefits in metastatic colorectal cancer, and its synergistic effect in combination with anti-angiogenic drugs in solid tumors has also been preliminarily confirmed.
The biological basis of combination therapy: Anti-angiogenic drugs can improve the hypoxic state of the tumor microenvironment, enhance the delivery efficiency of chemotherapy drugs, and simultaneously inhibit the infiltration of immunosuppressive cells. Their combination with chemotherapy or immunotherapy has potential synergistic effects. Preclinical studies have shown that anlotinib combined with fluoropyrimidine drugs can significantly inhibit the growth of esophageal cancer models by dual inhibition of tumor proliferation and angiogenesis pathways.
Based on the above background, this study intends to explore the efficacy and safety of Suyuan combined with anlotinib in the second-line treatment of recurrent and metastatic ESCC, aiming to provide new treatment options for patients.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with pathologically confirmed esophageal squamous cell carcinoma.
- •Clinical stage IIIB-C or IV according to the 8th edition of AJCC.
- •Having at least one measurable or evaluable lesion.
- •ECOG performance status score of 0-
- •Failed first-line standard treatment regimens.
- •Age ≥ 18 years.
- •Normal function of major organs.
- •Female subjects of childbearing age must undergo a pregnancy test within 3 days before the first dose with a negative result, and adopt effective contraceptive measures during the study period.
排除标准
- •Patients with other malignant tumors requiring treatment.
- •Patients with severe diseases of major organs such as heart, liver, and kidney.
- •Patients who have previously received treatment with anti-angiogenic monoclonal antibodies or small-molecule tyrosine kinase inhibitors.
- •Patients with an expected survival period of < 3 months.
- •Patients who have previously used fluoropyrimidine drugs (such as 5-FU, capecitabine, etc.).
- •Patients with Uncontrolled active infections (such as HIV, HCV, HBV, etc.).
- •Pregnant or lactating women.
- •Other circumstances deemed unsuitable for enrollment by the researcher.
研究组 & 干预措施
Trifluridine/tipiracil combined with Anlotinib Group
Trifluridine/tipiracil combined with Anlotinib for second-line treatment of recurrent and metastatic ESCC
干预措施: Combination therapy (COMB) (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: From date of therapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
The time interval from the day a patient starts receiving a certain treatment (or is randomized into a treatment regimen) to the occurrence of objective tumor progression (or death from any cause).
次要结局
- Overall Survival (OS)(From date of therapy until the date of death, assessed up to 24 months)
研究者
QiangfengWang
Principal Investigator
First Affiliated Hospital of Zhejiang University