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

Neoadjuvant Toripalimab and Paclitaxel/Cisplatin on Pathological Response in Oral Squamous Cell Carcinoma Patients: A Single-arm Phase I Trial

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University

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: 0-1 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 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

Experimental: Neoadjuvant therapy with Toripalimab, Paclitaxcel and 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.

Drug: Toripalimab; Neoadjuvant therapy with Toripalimab of 240mg, iv, qd, on day 1, 22; Other Names: Toripalimab for Injection; Drug: Paclitaxcel; Neoadjuvant therapy with Paclitaxcel of 260mg/m2, iv, qd, on day 1, 22; Other Names: Paclitaxel for Injection (Albumin Bound); Drug: Cisplatin; Neoadjuvant therapy with Cisplatin of 75mg/m2, iv, qd, on day 1, 22; Other Names: Cisplatin for Injection; Procedure: Radical surgery; Radical surgery will be performed on the 43th-48th 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 pathological diagnosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major pathological response	Major pathological response is based on the pathological examination on the post-operative specimens after neoadjuvant 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, MD, PhD, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2020
• Primary Completion (Actual): April 12, 2021
• Study Completion (Actual): September 30, 2023

Study Registration Dates

• First Submitted: July 14, 2020
• First Submitted That Met QC Criteria: July 14, 2020
• First Posted (Actual): July 16, 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; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Cisplatin
• Other Study ID Numbers: Illuminate trial

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No