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

NCT04393506 | Completed Phase 1 DMC

• 1 other identifier: Icemelting trial
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Oral Cancer; VEGFR2 Inhibitor; Programmed Cell Death 1 Inhibitor; Inductive Therapy

Outcome Measures

Primary Outcomes (1)

• Major pathologic response

  Major pathologic response is based on the pathological examination on the post-operative specimens after inductive therapy.

  One year

Secondary Outcomes (2)

• 2-year overall survival

  Two years

• 2-year tumor recurrence rate

  Two years

Study Arms (1)

Inductive therapy

OTHER

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

Drug: Camrelizumab; Drug: Apatinib; Procedure: Radical surgery; Radiation: Post-operative radiotherapy/chemoradiotherapy

Interventions

Camrelizumab DRUG

Inductive therapy with Camrelizumab of 200mg, iv, qd, on day 1, 15, 29.

Also known as: Humanized anti-PD-1 inhibitor

Inductive therapy

Apatinib DRUG

Inductive therapy with Apatinib of 250mg, po, qd, initiating on day 1, ending on the fifth day before surgery.

Also known as: VEGFR2 inhibitor

Inductive therapy

Radical surgery PROCEDURE

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

Inductive therapy

Post-operative radiotherapy/chemoradiotherapy RADIATION

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

Inductive therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shanghai Jiao Tong University School of Medicine: lead

Study Sites (1)

Shanghai Ninth People's Hospital

Shanghai, Shanghai Municipality, 200011, China

Location

Related Publications (1)

• 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.

  PMID: 36104359 DERIVED

MeSH Terms

Conditions

Mouth Neoplasms

Interventions

camrelizumab; apatinib; Chemoradiotherapy

Condition Hierarchy (Ancestors)

Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Study Officials

• Lai-ping Zhong, PHD

  Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 3, 2020
• First Posted: May 19, 2020
• Study Start: April 23, 2020
• Primary Completion: November 2, 2020
• Study Completion: November 10, 2023
• Last Updated: November 22, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)