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

Oral Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04473716
• Other study ID #: Illuminate trial
• Status: Completed
• Phase: Phase 1
• Start date: July 30, 2020
• Est. completion date: September 30, 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

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: September 30, 2023
• Est. primary completion date: April 12, 2021
• 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: 0-1 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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Toripalimab
Neoadjuvant therapy with Toripalimab of 240mg, iv, qd, on day 1, 22
• Paclitaxcel
Neoadjuvant therapy with Paclitaxcel of 260mg/m2, iv, qd, on day 1, 22
• Cisplatin
Neoadjuvant therapy with Cisplatin of 75mg/m2, iv, qd, on day 1, 22

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.

Locations

Country	Name	City	State
China	Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University	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 pathological response	Major pathological response is based on the pathological examination on the post-operative specimens after neoadjuvant 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