Neoadjuvant Toripalimab and Paclitaxel/Cisplatin on Pathological Response in Oral Squamous Cell Carcinoma Patients

Phase 1

Completed

• Conditions: Oral Cancer; Induction Chemotherapy; Programmed Cell Death 1 Inhibitor; Inductive Therapy
• Interventions: Drug: Toripalimab; Drug: Paclitaxcel; Drug: Cisplatin; Procedure: Radical surgery; Radiation: Post-operative radiotherapy/chemoradiotherapy

• Registration Number: NCT04473716
• Lead Sponsor: Shanghai Jiao Tong University School of Medicine

Brief Summary

The aim of this study is to use the combination of immune checkpoint inhibitor of Toripalimab, and chemotherapy agents of TP, as a neoadjuvant therapy to treat the patients with locally advanced OSCC, followed with radical surgery and post-operative radiotherapy/chemoradiotherapy, the major pathological 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

In patients with locally advanced oral squamous cell carcinoma (OSCC), comprehensive treatment is recommended, including surgery, radiotherapy, chemotherapy and others. Pre-operative neoadjuvant therapy can reduce tumor burden, increase organ preservation rate, and reduce distant metastasis rate. Pre-operative neoadjuvant therapy with paclitaxcel and cisplatin (TP) has been used as one of recommended protocols in patients with locally advanced head and neck squamous cell caricnoma, including OSCC. Anti-PD1/PD-L1 immunotherapies have achieved exciting clinical outcomes in several malignancies, such as lung cancer, breast cancer, and so on. Recently, pre-operative neoadjuvant therapy with combination of immunotherapy and chemotherapy agents has been used with good pathological response, which might transfer to good clinical prognosis in patients with malignancies. However, pre-operative neoadjuvant therapy with combination of anti-PD1 and TP in OSCC patients has not been reported. The innovation of this study is the combination of immune checkpoint inhibitor of Toripalimab, and chemotherapy agents of TP, as a neoadjuvant therapy to treat the patients with locally advanced OSCC, followed with radical surgery and post-operative radiotherapy/chemoradiotherapy, the major pathological 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 Timeline

• Study First Submitted: 2020-07-14
• Study First Submitted QC: 2020-07-14
• Study First Posted: 2020-07-16
• Study Start: 2020-07-30
• Primary Completion: 2021-04-12
• Study Completion: 2023-09-30
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-21
• Last Update Posted: 2023-11-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Eastern cooperative oncology group performance status (ECOG PS) score: 0-1 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
• Grade 3-4 allergic reactions to Toripalimab, paclitaxcel or cisplatin
• Active severe clinical infection (> CTCAE 5.0 version 2 infection)
• Difficult to control hypertension or cardiovascular disease with clinical significance (such as activity)-such as cerebrovascular accident (< 6 months before treatment), myocardial infarction (< 6 months before treatment), 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
• Chronic diseases requiring immunotherapy or hormone therapy
• 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
Neoadjuvant therapy with Toripalimab, Paclitaxcel and Cisplatin	Paclitaxcel	Pre-operative neoadjuvant therapy will be used with the combination of immune checkpoint inhibitor of Toripalimab, and chemotherapy agents of paclitaxcel and cisplatin in patients with locally advanced OSCC. After inductive therapy, the patients will receive radical surgery and post-operative radiotherapy/chemoradiotherapy.
Neoadjuvant therapy with Toripalimab, Paclitaxcel and Cisplatin	Radical surgery	Pre-operative neoadjuvant therapy will be used with the combination of immune checkpoint inhibitor of Toripalimab, and chemotherapy agents of paclitaxcel and cisplatin in patients with locally advanced OSCC. After inductive therapy, the patients will receive radical surgery and post-operative radiotherapy/chemoradiotherapy.
Neoadjuvant therapy with Toripalimab, Paclitaxcel and Cisplatin	Post-operative radiotherapy/chemoradiotherapy	Pre-operative neoadjuvant therapy will be used with the combination of immune checkpoint inhibitor of Toripalimab, and chemotherapy agents of paclitaxcel and cisplatin in patients with locally advanced OSCC. After inductive therapy, the patients will receive radical surgery and post-operative radiotherapy/chemoradiotherapy.
Neoadjuvant therapy with Toripalimab, Paclitaxcel and Cisplatin	Toripalimab	Pre-operative neoadjuvant therapy will be used with the combination of immune checkpoint inhibitor of Toripalimab, and chemotherapy agents of paclitaxcel and cisplatin in patients with locally advanced OSCC. After inductive therapy, the patients will receive radical surgery and post-operative radiotherapy/chemoradiotherapy.
Neoadjuvant therapy with Toripalimab, Paclitaxcel and Cisplatin	Cisplatin	Pre-operative neoadjuvant therapy will be used with the combination of immune checkpoint inhibitor of Toripalimab, and chemotherapy agents of paclitaxcel and cisplatin in patients with locally advanced OSCC. After inductive therapy, the patients will receive radical surgery and post-operative radiotherapy/chemoradiotherapy.

Primary Outcome Measures

Name	Time	Method
Major pathological response	One year	Major pathological response is based on the pathological examination on the post-operative specimens after neoadjuvant 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)

Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University; 🇨🇳 Shanghai, Shanghai, China