Toripalimab in Combined With Cetuximab，Chemotherapy for Conversion Therapy of Locally Nonresectable OCSCC

Toripalimab in Combination With Cetuximab，Cisplatin and 5-FU for Conversion Therapy of Locally Nonresectable Oral Cavity Squamous Cell Carcinoma （OCSCC）

This is a prospective, single center phase II clinical study with a planned enrollment of 33 patients. The main objective is to evaluate the efficacy and safety of the PD-1 inhibitor toripalimab combined with cetuximab, cisplatin, and 5-FU regimen in the treatment of locally advanced oral squamous cell carcinoma patients who are initially unresectable.

Study Overview

• Status: Recruiting
• Conditions: Squamous Cell Carcinoma of Head and Neck
• Intervention / Treatment: Drug: Toripalimab

Detailed Description

In the past decade, the treatment plan for non-surgical locally advanced HNSCC patients who are suitable for receiving synchronous radiotherapy and chemotherapy has remained unchanged, and innovative treatment methods are urgently needed. Based on the above research, immunotherapy combined with chemotherapy and immunotherapy combined with cetuximab have good efficacy and safety in non-surgical HNSCC patients. Therefore, combining PD-L1 antibodies with chemotherapy, surgery to further improve the efficacy of comprehensive treatment may become a new direction in tumor treatment. The achievement of pCR or MPR in conversion therapy is related to better OS and DFS outcomes in patients. In the era of immunotherapy, conversion therapy centered around surgery has become a hot topic in the field of treatment for locally advanced oral squamous cell carcinoma that cannot be surgically removed upon initial diagnosis.

There is no particularly preferred standard conversion chemotherapy regimen for patients with locally advanced head and neck squamous cell carcinoma that cannot be surgically removed initially. The combination of PD-1 inhibitor toripalimab, cetuximab, and chemotherapy may benefit the efficacy of these patients. Therefore, this prospective phase II clinical trial was designed to evaluate the efficacy and safety of PD-1 inhibitor toripalimab combined with chemotherapy and cetuximab conversion therapy in locally advanced oral squamous cell carcinoma patients who were initially unresectable.

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yulong Zheng, MD; Phone Number: 13588166206; Email: drzhengyu@126.com
• Study Contact Backup: Name: CHENG XIAO, MD; Phone Number: 87235896; Email: 21218159@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • Department of Medical Onocology, First Affiliated Hospital of Zhejiang University
      • Contact: Yulong Zheng, MD; Phone Number: 13588166206; Email: drzhengyu@126.com
      • Contact: CHENG XIAO, MD; Phone Number: 87235896; Email: 21218159@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed squamous cell carcinoma of tongue, floor of mouth, gingival, buccal
• Initial NCCN TNM stage III and IVA patients
• PS score 0-1 points
• Age≥18 years old
• Measurable lesions that meet RECIST 1.1 standards
• Normal function of important organs
• All patients must provide tissue specimens

Exclusion Criteria:

• Active, known or suspected autoimmune disease patients
• According to the judgment of the researcher, there are accompanying diseases that seriously endanger the safety of the subjects or affect the completion of the study by the patients
• Merge with other malignant tumors
• Subjects with known central nervous system metastasis and/or cancerous meningitis
• Uncontrolled pleural effusion, pericardial effusion, or ascites that require repeated drainage
• Received significant surgical treatment or obvious traumatic injury within the first 28 days of randomization
• Have experienced arterial/venous thrombotic events within the first 6 months of randomization, such as cerebrovascular accidents
• Individuals with a history of abuse of psychotropic substances who are unable to quit or have mental disorders
• Subjects with any severe and/or uncontrollable diseases
• Exclusion criteria related to concomitant medications
• Participated in other clinical trials within four weeks
• Have received preventive or attenuated vaccines within 4 weeks before the first administration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Toripalimab plus Cetuximab，chemotherapy group; All subjects received 2-cycle conversion therapy with the PD-1 inhibitor toripalimab combined with cetuximab, cisplatin, and 5-FU The dosage of medication used is as follows: Toripalimab: 240mg, Day1, Q3W；Cisplatin: 25mg/m2, Day1-3, Q3W；5-FU: 1000mg/m2, Day1-3, Q3W Cetuximab Day 1, 8, 15, Q3W, 400 mg/m2 initial dose; Afterwards, 250 mg/m2 per week

Drug: Toripalimab; This study was conducted on 30 patients with initially unresectable locally advanced head and neck squamous cell carcinoma who underwent two cycles of PD-1 antibody (trepril monoclonal antibody) combined with fluorouracil, cisplatin, and cetuximab conversion therapy. The feasibility of radical surgery should be evaluated before surgical treatment.Three patients were enrolled in the safe induction period before the study began. The dosage of medication used is as follows: Toripalimab: 240mg, Day1, Q3W Cisplatin: 25mg/m2, Day1-3, Q3W（every 3 weeks） 5-FU: 1000mg/m2, Day1-3, Q3W Cetuximab Day 1, 8, 15, Q3W, 400 mg/m2 initial dose; Afterwards, 250 mg/m2 per week; Other Names: Drug: Cetuximab; Drug: Cisplatin; Drug: 5-FU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major pathological response（MPR）	To determine the major pathological response rate, defined as <10% viable tumor in the resection specimen, after two cycles of neoadjuvant Toripalimab Plus Cetuximab，Cisplatin and 5-FU in patients with Nonresectable Oral Cavity Squamous Cell Carcinoma （OCSCC）	through study completion; an average of 1 year

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University
• Investigators: Principal Investigator: Yulong Zheng, MD, First affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2023
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: October 7, 2023
• First Submitted That Met QC Criteria: October 7, 2023
• First Posted (Actual): October 13, 2023

Study Record Updates

• Last Update Posted (Actual): October 13, 2023
• Last Update Submitted That Met QC Criteria: October 7, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cisplatin; Cetuximab
• Other Study ID Numbers: IIT20220085C-R1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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