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

Oral Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04393506
• Other study ID #: Icemelting trial
• Status: Completed
• Phase: Phase 1
• Start date: April 23, 2020
• Est. completion date: November 10, 2023

Study information

• Verified date: November 2023
• Source: Shanghai Jiao Tong University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: November 10, 2023
• Est. primary completion date: November 2, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Inductive Therapy
• Mouth Neoplasms
• Oral Cancer
• Programmed Cell Death 1 Inhibitor
• Squamous Cell Carcinoma of Head and Neck
• VEGFR2 Inhibitor

Intervention

Drug:
• Camrelizumab
Inductive therapy with Camrelizumab of 200mg, iv, qd, on day 1, 15, 29.
• Apatinib
Inductive therapy with Apatinib of 250mg, po, qd, initiating on day 1, ending on the fifth day before surgery.

Procedure:
• Radical surgery
Radical surgery will be performed on the 42th-45th after initiation of inductive therapy

Radiation:
• Post-operative radiotherapy/chemoradiotherapy
Post-operative radiotherapy/chemoradiotherapy will be performed within 1.5 months after radical surgery, depending on the post-operative pathologic diagnosis.

Locations

Country	Name	City	State
China	Shanghai Ninth People's Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Jiao Tong University School of Medicine

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major pathologic response	Major pathologic response is based on the pathological examination on the post-operative specimens after inductive therapy.	One year
Secondary	2-year overall survival	The overall survival time refers to the time from initiating inductive therapy to death due to any cause.	Two years
Secondary	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