Clinical trial NCT06130332: Neoadjuvant Tirellizumab Combined With Chemotherapy for Early Oral Squamous Cell Carcinoma(HNC-SYSU-004)
Official title: A Single-center Exploratory Clinical Study of Neoadjuvant Tirellizumab Combined With Chemotherapy for Early Oral Squamous Cell Carcinoma (cT1-2N0M0)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Oral Cancer
PD-1
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2023-11-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Surgery is usually the first choice for early-stage oral squamous cell carcinoma (OSCC). However, there is currently a lack of consensus on whether patients with clinically negative cervical lymph nodes (N0) should undergo elective neck dissection (END) at the same time. About 20-30% of cT1-2N0M0 oral cancer patients have occult lymph node metastasis, and existing examination methods cannot accurately predict occult cervical lymph node metastasis. Therefore, most clinical retrospective and prospective studies recommend END for cN0 patients. Previous studies have found that no cancer cells were found in the cervical lymph nodes of 70% of patients after END. This unselective END can cause patients with accessory nerve dysfunction, neck scars, etc., and prolong hospitalization and surgery time. Exploring the treatment model for patients with early-stage oral squamous cell carcinoma is an urgent problem that needs to be solved. This study intends to conduct a study on the neoadjuvant treatment of tislelizumab, carboplatin, and albumin-bound paclitaxel. After neoadjuvant immunotherapy in patients with early-stage oral cancer (T1-2N0M0), the primary tumor is treated with standard surgical treatment. Comparison with A single-center exploratory clinical study of traditional oral cancer radical resection + selective neck lymphadenectomy was conducted to explore its effectiveness through the difference in 2-year disease-free survival (DFS).

This research plan covers 40 patients with early-stage oral squamous cell carcinoma. They will be randomly divided into tislelizumab, chemotherapy combined with surgery (experimental group) and traditional surgery (control group) in a 1:1 ratio. The patients' tumors will be collected. Tissues, adjacent cancer tissues, whole blood samples, saliva samples, and matrix samples were used to observe the changes in imaging and pathology compared with treatment. At the same time, the clinical information of the patients was collected, such as quality of life indicators such as judgment function, pathological grading, staging, treatment, Spine, serology, imaging, etc., mainly to evaluate the 2-year event-free survival (EFS) between the experimental group and Weather Forecast, and the 3-year overall survival (OS) and patient quality of life between the experimental group and Weather Forecast.


Eligibility criteria: Inclusion Criteria:

* Patients with early oral squamous cell carcinoma diagnosed as T1-2N0M0 according to the eighth edition of AJCC classification;
* No history of other malignant tumors;
* 18-75 years old;
* Baseline inspection is normal:

  1. The absolute value of neutrophil (ANC) ≥1.5x109/L in the past 14 days without the use of granulocyte colony-stimulating factor;
  2. Platelets ≥100×109/L without blood transfusion in the past 14 days;
  3. In the case of no blood transfusion or use of erythropoietin in the last 14 days, hemoglobin \&gt; 9g/dL;
  4. Total bilirubin ≤1.5× upper limit of normal (ULN);
  5. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) in ≤2.5×ULN (patients with liver metastases allowed ALT or AST ≤5×ULN);
  6. Serum creatinine ≤1.5×ULN and creatinine clearance (calculated by Cockcroft-Gault formula) ≥60 ml/min;
  7. Good coagulation function, defined as International standardized ratio (INR) or prothrombin time (PT) ≤1.5 times ULN;
  8. Normal thyroid function, defined as thyroid stimulating hormone (TSH) within the normal range. If baseline TSH is outside the normal range, subjects with total T3 (or FT3) and FT4 within the normal range can also be enrolled;
  9. The myocardial enzyme profile is within the normal range (if the researchers comprehensively judge that the simple laboratory abnormality is not clinically significant, it is also allowed to enter the group);
  10. For female subjects of reproductive age, a urine or serum pregnancy test should be performed within 3 days prior to receiving the first study drug administration (day 1 of cycle 1) and the result is negative. If the urine pregnancy test results cannot be confirmed as negative, a blood pregnancy test is requested. Women of non-reproductive age were defined as at least one year after menopause or having undergone surgical sterilization or hysterectomy;
  11. If there is a risk of conception, all subjects (male or female) are required to use contraception with an annual failure rate of less than 1% for the entire duration of treatment up to 120 days after the last study drug administration (or 180 days after the last chemotherapy drug administration).
* Sign informed consent.

Exclusion Criteria:

* Other malignant tumors are diagnosed, or oral cancer is not the beginning of neoadjuvant therapy;
* Prior to treatment, an active autoimmune disease requiring systemic treatment (such as the use of disease-modifying drugs, glucocorticoids, or immunosuppressants) has occurred within the previous 2 years. Replacement therapies (such as thyroxine, insulin, or physiologic glucocorticoids for adrenal or pituitary insufficiency) are not considered systemic therapy;
* known allogeneic organ transplantation (other than corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
* Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive);
* untreated active hepatitis B (defined as HBsAg positive and HBV-DNA copy number detected greater than the upper limit of normal value in the laboratory of the study center);

Note: Hepatitis B subjects who meet the following criteria can also be enrolled:

1. HBV viral load \&lt before first dosing; 1000 copies /ml (200 IU/ml), subjects should receive anti-HBV therapy throughout study treatment to avoid viral reactivation;
2. For subjects with anti-HBC (+), HBsAg (-), anti-HBS (-) and HBV viral load (-), prophylactic anti-HBV therapy is not required, but close monitoring of viral reactivation is required;

   * active HCV-infected subjects (HCV antibody positive and HCV-RNA levels above the lower limit of detection);
   * Pregnant or lactating women;
   * The presence of any serious or uncontrolled systemic disease, such as:

1) The resting electrocardiogram has major abnormal rhythm, conduction or morphology, such as complete left bundle branch block, heart block above Ⅱ degree, ventricular arrhythmia or atrial fibrillation; 2) Unstable angina pectoris, congestive heart failure, New York Heart Association (NYHA) grade ≥ 2 chronic heart failure;

Primary outcomes:
measure: Disease-free survival
timeFrame: 2 years
measure: Quality of life assessed by EORTC QLQ-H&N35.
timeFrame: 2 years
Secondary outcomes:
measure: Overall survival(OS)
timeFrame: 5 years
measure: Major pathologic response
timeFrame: 6 weeks
measure: Objective response rate, ORR
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun yat-sen memorial hospital
state: Guangdong
Study officials:
References: