Neoadjuvant Sintilimab Plus Chemotherapy for cT2N0M0 Oral Squamous Cell Carcinoma

This study is a superiority multi-center, open-label, phase III randomized controlled trial. It will further verify the clinical value of xidili single-antibody combined with chemotherapy (albumin paclitaxel and carboplatin) in neoadjuvant treatment for operable cT2N0M0 early oral squamous cell carcinoma (Oral Squamous Cell Carcinoma, OSCC) patients in terms of improving long-term survival and pathological remission. The study subjects are patients aged 18-75 years, diagnosed with cT2N0M0 stage (8th edition AJCC staging as stage II) OSCC by pathology, with ECOG score of 0-1, good organ function, and meeting laboratory standards (ANC ≥ 1.5 × 10⁹/L, Hb \> 90g/L, CrCl ≥ 60ml/min, ALT/AST ≤ 2.5 × ULN); Exclusion criteria include previous immunotherapy with immune checkpoint inhibitors, active autoimmune diseases, poorly controlled comorbidities, high viral load infection of HBV/HCV, etc.; Patients with surgical resection conditions and signing informed consent will be enrolled. The subjects were randomly divided into two groups at a ratio of 1:1: The experimental group received neoadjuvant treatment with xidili single-antibody combined with albumin paclitaxel and carboplatin for 2-3 cycles followed by surgery (primary lesion resection + I-III region cervical lymph node dissection), while the control group received standard treatment (direct surgery). The primary endpoint of the study is the 3-year event-free survival rate (Event-Free Survival rate, EFS rate), and secondary endpoints include overall survival rate (Overall survival rate, OS rate), major pathological response rate (Major Pathological Response, MPR), complete pathological response rate (Complete Pathological Response, pCR), objective response rate (Objective Response Rate, ORR), safety analysis (Treatment-Related Adverse Event, TRAE), and postoperative lymph node positive rate (Lymph Node Positivity rate, LNP rate). The sample size was calculated based on the Log-rank test, referring to the prospective clinical baseline data of standard surgical treatment for early oral cancer, setting the 3-year EFS rate of the control group at 80%, assuming that the experimental group can be improved to 90% (HR = 0.47), setting a two-sided α = 0.05, efficacy 80%, and follow-up dropout rate 10%, a total of 300 patients (150 in each group) need to be enrolled. This study will provide high-quality evidence-based evidence for optimizing the treatment strategy for cT2N0M0 early high-risk oral squamous cell carcinoma, improving the pathological response rate and long-term recurrence-free survival.

Sex

All

Minimum age

18 Years

Maximum age

75 Years

Inclusion Criteria:

1. Histologically confirmed primary squamous cell carcinoma of the oral cavity.
2. Clinical stage cT2N0M0 according to the AJCC 8th edition staging system.
3. Age between 18 and 75 years old.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Deemed eligible for radical surgical resection of the primary tumor and regional lymph nodes.
6. Adequate organ function within 14 days prior to randomization:

   * Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
   * Platelets \>= 100 x 10\^9/L
   * Hemoglobin \>= 9.0 g/dL
   * Total bilirubin \<= 1.5 x upper limit of normal (ULN)
   * AST and ALT \<= 2.5 x ULN
   * Serum creatinine \<= 1.5 x ULN or creatinine clearance \>= 50 mL/min
7. Voluntary written informed consent provided by the patient or legal representative.

Exclusion Criteria:

1. Presence of regional lymph node metastasis or distant metastasis (cN+ or M1).
2. Prior systemic antitumor therapy, radiotherapy, or immunotherapy for head and neck cancer.
3. History of other active malignant neoplasms within the past 5 years (except adequately treated non-melanoma skin cancer or carcinoma in situ).
4. Active autoimmune disease or history of severe autoimmune disease requiring systemic corticosteroids or immunosuppressive agents.
5. Severe cardiovascular disease, including unstable angina, myocardial infarction within 6 months, or uncontrolled heart failure (NYHA Class III/IV).
6. Active infection requiring systemic intravenous antimicrobial treatment.
7. Known history of severe allergy or hypersensitivity to sintilimab, albumin-bound paclitaxel, carboplatin, or their excipients.
8. Pregnant or breastfeeding women, or patients of childbearing potential unwilling to use effective contraception during the study and for 6 months after the last dose.
9. Any underlying medical condition or psychiatric disorder that, in the opinion of the investigator, would jeopardize participant safety or trial compliance.