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

Phase 1

Completed

• Conditions: VEGFR2 Inhibitor; Inductive Therapy; Programmed Cell Death 1 Inhibitor; Oral Cancer
• Interventions: Drug: Camrelizumab; Drug: Apatinib; Procedure: Radical surgery; Radiation: Post-operative radiotherapy/chemoradiotherapy

• Registration Number: NCT04393506
• Lead Sponsor: Shanghai Jiao Tong University School of Medicine

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-04-23
• Study First Submitted: 2020-05-03
• Study First Submitted QC: 2020-05-16
• Study First Posted: 2020-05-19
• Primary Completion: 2020-11-02
• Status Verified: 2023-11
• Study Completion: 2023-11-10
• Last Update Submitted: 2023-11-21
• Last Update Posted: 2023-11-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Inductive therapy	Post-operative radiotherapy/chemoradiotherapy	Inductive therapy with Camrelizumab and Apatinib, followed by radical surgery and post-operative radiotherapy/chemoradiotherapy.
Inductive therapy	Radical surgery	Inductive therapy with Camrelizumab and Apatinib, followed by radical surgery and post-operative radiotherapy/chemoradiotherapy.
Inductive therapy	Apatinib	Inductive therapy with Camrelizumab and Apatinib, followed by radical surgery and post-operative radiotherapy/chemoradiotherapy.
Inductive therapy	Camrelizumab	Inductive therapy with Camrelizumab and Apatinib, followed by radical surgery and post-operative radiotherapy/chemoradiotherapy.

Primary Outcome Measures

Name	Time	Method
Major pathologic response	One year	Major pathologic response is based on the pathological examination on the post-operative specimens after inductive therapy.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Shanghai Ninth People's Hospital; 🇨🇳 Shanghai, Shanghai, China