Neoadjuvant Toripalimab and Paclitaxel/Cisplatin on Pathological Response in Oral Squamous Cell Carcinoma Patients
Primary Purpose
Oral Cancer, Induction Chemotherapy, Programmed Cell Death 1 Inhibitor
Status
Active
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Toripalimab
Paclitaxcel
Cisplatin
Radical surgery
Post-operative radiotherapy/chemoradiotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Oral Cancer
Eligibility Criteria
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
Sites / Locations
- Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Neoadjuvant therapy with Toripalimab, Paclitaxcel and Cisplatin
Arm Description
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.
Outcomes
Primary Outcome Measures
Major pathological response
Major pathological response is based on the pathological examination on the post-operative specimens after neoadjuvant therapy.
Secondary Outcome Measures
2-year overall survival
The overall survival time refers to the time from initiating inductive therapy to death due to any cause.
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.
Full Information
NCT ID
NCT04473716
First Posted
July 14, 2020
Last Updated
October 4, 2022
Sponsor
Shanghai Jiao Tong University School of Medicine
1. Study Identification
Unique Protocol Identification Number
NCT04473716
Brief Title
Neoadjuvant Toripalimab and Paclitaxel/Cisplatin on Pathological Response in Oral Squamous Cell Carcinoma Patients
Official Title
Neoadjuvant Toripalimab and Paclitaxel/Cisplatin on Pathological Response in Oral Squamous Cell Carcinoma Patients: A Single-arm Phase I Trial
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 30, 2020 (Actual)
Primary Completion Date
April 12, 2021 (Actual)
Study Completion Date
September 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Jiao Tong University School of Medicine
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oral Cancer, Induction Chemotherapy, Programmed Cell Death 1 Inhibitor, Inductive Therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Neoadjuvant therapy with Toripalimab, Paclitaxcel and Cisplatin
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Toripalimab
Other Intervention Name(s)
Toripalimab for Injection
Intervention Description
Neoadjuvant therapy with Toripalimab of 240mg, iv, qd, on day 1, 22
Intervention Type
Drug
Intervention Name(s)
Paclitaxcel
Other Intervention Name(s)
Paclitaxel for Injection (Albumin Bound)
Intervention Description
Neoadjuvant therapy with Paclitaxcel of 260mg/m2, iv, qd, on day 1, 22
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Cisplatin for Injection
Intervention Description
Neoadjuvant therapy with Cisplatin of 75mg/m2, iv, qd, on day 1, 22
Intervention Type
Procedure
Intervention Name(s)
Radical surgery
Intervention Description
Radical surgery will be performed on the 43th-48th after initiation of inductive therapy.
Intervention Type
Radiation
Intervention Name(s)
Post-operative radiotherapy/chemoradiotherapy
Intervention Description
Post-operative radiotherapy/chemoradiotherapy will be performed within 1.5 months after radical surgery, depending on the post-operative pathological diagnosis.
Primary Outcome Measure Information:
Title
Major pathological response
Description
Major pathological response is based on the pathological examination on the post-operative specimens after neoadjuvant therapy.
Time Frame
One year
Secondary Outcome Measure Information:
Title
2-year overall survival
Description
The overall survival time refers to the time from initiating inductive therapy to death due to any cause.
Time Frame
Two years
Title
2-year tumor recurrence rate
Description
The tumor recurrence rate is calculated using the number of patients with tumor recurrence divided by the total number of patients.
Time Frame
Two years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lai-ping Zhong, MD, PhD
Organizational Affiliation
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University
City
Shanghai
State/Province
Shanghai
Country
China
12. IPD Sharing Statement
Learn more about this trial
Neoadjuvant Toripalimab and Paclitaxel/Cisplatin on Pathological Response in Oral Squamous Cell Carcinoma Patients
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