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

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200011
      • Shanghai Ninth People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Inductive therapy; Inductive therapy with Camrelizumab and Apatinib, followed by radical surgery and post-operative radiotherapy/chemoradiotherapy.

Drug: Camrelizumab; Inductive therapy with Camrelizumab of 200mg, iv, qd, on day 1, 15, 29.; Other Names: Humanized anti-PD-1 inhibitor; Drug: Apatinib; Inductive therapy with Apatinib of 250mg, po, qd, initiating on day 1, ending on the fifth day before surgery.; Other Names: VEGFR2 inhibitor; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine
• Investigators: Principal Investigator: Lai-ping Zhong, PHD, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

Publications and helpful links

General Publications

• Ju WT, Xia RH, Zhu DW, Dou SJ, Zhu GP, Dong MJ, Wang LZ, Sun Q, Zhao TC, Zhou ZH, Liang SY, Huang YY, Tang Y, Wu SC, Xia J, Chen SQ, Bai YZ, Li J, Zhu Q, Zhong LP. A pilot study of neoadjuvant combination of anti-PD-1 camrelizumab and VEGFR2 inhibitor apatinib for locally advanced resectable oral squamous cell carcinoma. Nat Commun. 2022 Sep 14;13(1):5378. doi: 10.1038/s41467-022-33080-8.

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2020
• Primary Completion (Actual): November 2, 2020
• Study Completion (Actual): November 10, 2023

Study Registration Dates

• First Submitted: May 3, 2020
• First Submitted That Met QC Criteria: May 16, 2020
• First Posted (Actual): May 19, 2020

Study Record Updates

• Last Update Posted (Estimated): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Stomatognathic Diseases; Mouth Diseases; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Mouth Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Apatinib; Immune Checkpoint Inhibitors
• Other Study ID Numbers: Icemelting trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No