Inductive Camrelizumab and Apatinib for Patients With Locally Advanced and Resectable Oral Squamous Cell Carcinoma: A Single-arm Phase I Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Major pathologic response
研究概览
简要总结
In patients with locally advanced oral squamous cell carcinoma (OSCC), due to the large tumor burden and neck lymph node metastasis, comprehensive treatment is recommended, including surgery, radiotherapy, chemotherapy and others. Pre-operative inductive therapy can reduce tumor volume, increase organ retention rate, and reduce distant metastasis rate. Vascular endothelial growth factor (VEGF) receptor in head and neck squamous cell carcinoma is over-expressed and associated with disease invasion and poor prognosis. The use of targeted therapy against VEGF can not only inhibit tumor neovascularization, but also make the effectiveness of chemotherapeutic agents. VEGF and VEGFR are closely related to immune escape. Tumor growth requires new blood vessels to supply nutrients and oxygen, and VEGF can stimulate neovascularization. However, tumor neovascularization is often abnormal and distorted, which prevents immune active substances from reaching the tumor site. After tumor hypoxia, high expression of VEGF will induce tumor cells to express programmed cell death protein-1 (PD-1), which further leads to immune escape. Targeted drugs against angiogenesis can relieve immunosuppression to a certain extent, and theoretically have a synergistic effect with anti-PD-1 immunotherapy. The innovation of this study is the combination of immune checkpoint inhibitor, Camrelizumab, and targeted drug against VEGFR, Apatinib, as an inductive therapy to treat the patients with locally advanced OSCC, followed with radical surgery and post-operative radiotherapy/chemoradiotherapy, the major pathologic response and safety will be evaluated as the primary surrogate endpoints, the 2-year survival rate and local recurrence rate will be the second endpoints.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eastern cooperative oncology group performance status (ECOG PS) score: 0-2 points
- •Pathological diagnosis of oral squamous cell carcinoma (including tongue, gums, cheeks, mouth floor, hard palate, posterior molar region)
- •Clinical stage of III/IVA (AJCC 2018)
- •Blood routine: white blood cells> 3,000/mm3, hemoglobin> 8g/L, platelets> 80,000/mm3
- •Liver function: Alanine Transaminase/Aspartate Transaminase <2.5 times the upper limit of normal, bilirubin <1.5 times the upper limit of normal
- •Renal function: serum creatinine <1.5 times the upper limit of normal
- •Sign the informed consent
排除标准
- •There are still unresolved toxic reactions above CTCAE level 2 caused by previous anti-cancer treatment
- •Obvious cardiovascular abnormalities [such as myocardial infarction, superior vena cava syndrome, heart disease of grade 2 or higher diagnosed according to the classification criteria of the New York Heart Association (NYHA) 3 months before enrollment]
- •Active severe clinical infection (> CTCAE 5.0 version 2 infection)
- •Difficult to control hypertension (systolic blood pressure> 150 mmHg and / or diastolic blood pressure> 90 mmHg) or cardiovascular disease with clinical significance (such as activity)-such as cerebrovascular accident (≤ 6 months before randomization), myocardial infarction (≤6 months before randomization), unstable angina, New York Cardiology Society (NYHA Appendix 5) congestive heart failure grade II or above, or severe arrhythmia that cannot be controlled with drugs or has potential impact on experimental treatment
- •Women during pregnancy or lactation
- •Participated in other clinical studies within 30 days before enrollment
- •Other circumstances that the investigator thinks are not suitable for participating in the study
研究组 & 干预措施
Inductive therapy
Inductive therapy with Camrelizumab and Apatinib, followed by radical surgery and post-operative radiotherapy/chemoradiotherapy.
干预措施: Camrelizumab (Drug)
Inductive therapy
Inductive therapy with Camrelizumab and Apatinib, followed by radical surgery and post-operative radiotherapy/chemoradiotherapy.
干预措施: Apatinib (Drug)
Inductive therapy
Inductive therapy with Camrelizumab and Apatinib, followed by radical surgery and post-operative radiotherapy/chemoradiotherapy.
干预措施: Radical surgery (Procedure)
Inductive therapy
Inductive therapy with Camrelizumab and Apatinib, followed by radical surgery and post-operative radiotherapy/chemoradiotherapy.
干预措施: Post-operative radiotherapy/chemoradiotherapy (Radiation)
结局指标
主要结局
Major pathologic response
时间窗: One year
Major pathologic response is based on the pathological examination on the post-operative specimens after inductive therapy.
次要结局
- 2-year overall survival(Two years)
- 2-year tumor recurrence rate(Two years)
研究者
Lai-ping Zhong
Principal Investigator
Shanghai Jiao Tong University School of Medicine