Inductive Camrelizumab and Apatinib for Patients With Locally Advanced and Resectable Oral Squamous Cell Carcinoma

Study Overview
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Brief Summary
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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.

Official Title
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Inductive Camrelizumab and Apatinib for Patients With Locally Advanced and Resectable Oral Squamous Cell Carcinoma: A Single-arm Phase I Trial

Conditions
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Oral Cancer, VEGFR2 Inhibitor, Programmed Cell Death 1 Inhibitor, Inductive Therapy

Intervention / Treatment
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* Drug: Camrelizumab
* Drug: Apatinib
* Procedure: Radical surgery
* Radiation: Post-operative radiotherapy/chemoradiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Inductive therapy<br>Inductive therapy with Camrelizumab and Apatinib, followed by radical surgery and post-operative radiotherapy/chemoradiotherapy. | Drug: Camrelizumab<br>* Inductive therapy with Camrelizumab of 200mg, iv, qd, on day 1, 15, 29.<br>* Other names: Humanized anti-PD-1 inhibitor;Drug: Apatinib<br>* Inductive therapy with Apatinib of 250mg, po, qd, initiating on day 1, ending on the fifth day before surgery.<br>* Other names: VEGFR2 inhibitor;Procedure: Radical surgery<br>* Radical surgery will be performed on the 42th-45th after initiation of inductive therapy<br>Radiation: Post-operative radiotherapy/chemoradiotherapy<br>* Post-operative radiotherapy/chemoradiotherapy will be performed within 1.5 months after radical surgery, depending on the post-operative pathologic diagnosis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major pathologic response | Major pathologic response is based on the pathological examination on the post-operative specimens after inductive therapy. | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year overall survival | The overall survival time refers to the time from initiating inductive therapy to death due to any cause. | Two years | 
| 2-year tumor recurrence rate | The tumor recurrence rate is calculated using the number of patients with tumor recurrence divided by the total number of patients. | Two years |