This is a multicenter, open-label, randomized phase III clinical trial evaluating perioperative treatment with sintilimab combined with chemotherapy in patients with locally advanced oral squamous cell carcinoma. Despite standard treatment with surgery followed by postoperative radiotherapy or chemoradiotherapy, patients with locally advanced oral squamous cell carcinoma remain at high risk of recurrence or metastasis. Recent evidence, including results from the KEYNOTE-689 study, suggests that perioperative immunotherapy may improve survival outcomes, and this approach has been incorporated into NCCN guidelines. Combining immunotherapy with chemotherapy may further improve prognosis in this patient population. Eligible participants will be randomly assigned to either an experimental group or a control group. The experimental group will receive neoadjuvant sintilimab combined with chemotherapy followed by surgery and postoperative treatment based on pathological response. Patients with major pathological response (MPR) will receive adjuvant sintilimab, while patients without MPR will receive postoperative radiotherapy or concurrent chemoradiotherapy combined with sintilimab. The control group will receive standard treatment consisting of surgery followed by postoperative radiotherapy or chemoradiotherapy as clinically indicated. The primary objective of the study is to compare event-free survival between the two groups. Secondary objectives include overall survival, pathological response, safety, and treatment-related adverse events. The results of this study may help optimize perioperative treatment strategies and improve outcomes for patients with locally advanced oral squamous cell carcinoma.
Oral squamous cell carcinoma (OSCC) is one of the most common malignancies of the head and neck region. A substantial proportion of patients present with locally advanced disease at diagnosis and remain at high risk of recurrence or metastasis despite radical surgery followed by postoperative radiotherapy or concurrent chemoradiotherapy. Previous studies have shown that conventional neoadjuvant or adjuvant chemotherapy provides limited benefit in improving long-term survival outcomes. Recent advances in immunotherapy have demonstrated significant efficacy in recurrent or metastatic head and neck squamous cell carcinoma, and emerging evidence supports the role of perioperative immunotherapy in resectable disease. The KEYNOTE-689 study demonstrated that perioperative immunotherapy could improve event-free survival in patients with locally advanced, resectable head and neck squamous cell carcinoma, leading to the incorporation of this strategy into the National Comprehensive Cancer Network (NCCN) guidelines. However, further optimization of perioperative treatment strategies is required to enhance pathological response and survival outcomes, particularly in patients with locally advanced OSCC. This study is a multicenter, open-label, randomized phase III clinical trial designed to evaluate the efficacy and safety of perioperative sintilimab combined with chemotherapy compared with standard treatment (surgery with or without postoperative radiotherapy or chemoradiotherapy) in patients with locally advanced OSCC. Eligible patients will be randomized in a 1:1 ratio to either the experimental group or the control group. Patients in the experimental group will receive neoadjuvant sintilimab combined with chemotherapy prior to definitive surgical resection. Postoperative treatment will be stratified according to pathological response. Patients achieving major pathological response (MPR) will receive adjuvant sintilimab for at least six cycles or until unacceptable toxicity. Patients without MPR will receive postoperative radiotherapy or concurrent chemoradiotherapy sequentially combined with sintilimab for at least six cycles or until unacceptable toxicity. Patients in the control group will receive standard treatment consisting of surgical resection followed by postoperative radiotherapy or concurrent chemoradiotherapy as clinically indicated. The primary endpoint of the study is event-free survival. Secondary endpoints include overall survival, pathological response to treatment, safety, and treatment-related adverse events. This study is expected to provide high-level evidence to optimize perioperative treatment strategies and improve clinical outcomes for patients with locally advanced oral squamous cell carcinoma.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
104
Neoadjuvant sintilimab combined with TP regimen followed by radical surgery and risk-stratified adjuvant therapy (low-risk: sintilimab monotherapy; high-risk: radiotherapy or concurrent chemoradiotherapy followed by sequential sintilimab).
Participants undergo radical surgical resection as primary treatment, followed by postoperative radiotherapy or concurrent chemoradiotherapy according to pathological risk factors and standard clinical practice.
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Guangzhou, Guangdong, China
RECRUITINGEvent-Free Survival (EFS)
Event-free survival is defined as the time from randomization to the first occurrence of disease progression, local or distant recurrence, second primary malignancy, or death from any cause, whichever occurs first.
Time frame: 2 years
overall survival(OS)
Overall survival (OS) was defined as the time from randomization to death from any cause.
Time frame: 2 years and 5 years.
pathological complete response(pCR)
Pathological complete response (pCR) is defined as the absence of residual viable tumor cells on microscopic examination in the resected primary tumor and lymph nodes, with all evaluated lymph nodes being negative. The pCR rate is calculated as the proportion of participants achieving pCR among all enrolled participants. The pCR rate is expressed as a percentage and its 95% confidence interval is estimated using the exact binomial distribution.
Time frame: At the time of definitive surgery
Major Pathological Response (MPR)
Major pathological response (MPR) is defined as the presence of 10% or less residual viable tumor cells in the resected primary tumor specimen on microscopic examination after neoadjuvant treatment, regardless of lymph node status. The MPR rate is calculated as the proportion of participants achieving MPR among all enrolled participants. The MPR rate is expressed as a percentage and its 95% confidence interval is estimated using the exact binomial distribution.
Time frame: At the time of definitive surgery
Treatment-related adverse events(TRAE)
Treatment-related adverse events (TRAEs) are defined as adverse events that are considered by the investigator to be possibly, probably, or definitely related to the study treatment, including sintilimab, chemotherapy, surgery, radiotherapy, or chemoradiotherapy. Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 6.0. The incidence, severity, and type of TRAEs will be summarized and analyzed.
Time frame: through study completion, an average of 1 year
Radiologic assessments
Radiologic assessments are performed to evaluate tumor response using contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI). Tumor response is assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, based on independent radiologic review.
Time frame: Baseline and preoperative
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.