Neoadjuvant Tirellizumab Combined With Chemotherapy for Early Oral Squamous Cell Carcinoma(HNC-SYSU-004)

NCT ID: NCT06130332

Last Updated: 2023-11-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-01
• Study Completion Date: 2030-08-31

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.

Conditions

Oral Cancer; PD-1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PD-1 with chemotherapy

Tirellizumab, Carboplatin,albumin-bound paclitaxel Patients receive Tirellizumab IV on day 1, albumin-bound paclitaxel IV on day 1 and carboplatin IV on day 1 . Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Then surgery.

Intervention: Drug: Tirellizumab, Carboplatin, albumin-bound paclitaxel:2 cycles

Surgery：Enlarged local excision，excision with the safe margin 1.0-1.5cm away from the original tumor

Group Type: EXPERIMENTAL

PD-1 with chemotherapy

Intervention Type: DRUG

Tirellizumab+Carboplatin+albumin-bound paclitaxel:2 courses Tirellizumab,+Carboplatin+albumin-bound paclitaxel Tirellizumab (IV), dose= 200mg , day=1 , cycle length: 21 days. Carboplatin (IV), dose=300mg/m2, day= 1, cycle length: 21 days. albumin-bound paclitaxel (IV), dose=260mg/m2, day= 1, cycle length: 21 days.

Intervention: Drug: Tirellizumab, Carboplatin, albumin-bound paclitaxel:2 cycles Surgery：Enlarged local excision，excision with the safe margin 1.0-1.5cm away from the original tumor

upright surgery

Surgery：Primary resection，excision with the safe margin 1.0-1.5cm away from the original tumor

selective neck dissection:I II III region neck dissection

Group Type: OTHER

upright surgery

Intervention Type: PROCEDURE

Surgery：Primary resection，excision with the safe margin 1.0-1.5cm away from the original tumor

selective neck dissection:I II III region neck dissection

Interventions

PD-1 with chemotherapy

Tirellizumab+Carboplatin+albumin-bound paclitaxel:2 courses Tirellizumab,+Carboplatin+albumin-bound paclitaxel Tirellizumab (IV), dose= 200mg , day=1 , cycle length: 21 days. Carboplatin (IV), dose=300mg/m2, day= 1, cycle length: 21 days. albumin-bound paclitaxel (IV), dose=260mg/m2, day= 1, cycle length: 21 days.

Intervention: Drug: Tirellizumab, Carboplatin, albumin-bound paclitaxel:2 cycles Surgery：Enlarged local excision，excision with the safe margin 1.0-1.5cm away from the original tumor

Intervention Type: DRUG

upright surgery

Surgery：Primary resection，excision with the safe margin 1.0-1.5cm away from the original tumor

selective neck dissection:I II III region neck dissection

Intervention Type: PROCEDURE

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 > 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;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Sun yat-sen memorial hospital

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Facility Contacts

Haotian Cao, MD

Role: primary

caobleat@hotmail.com

008618583879908

Qunxing Li, MD

Role: backup

liqx350@126.com

008618320699771

Other Identifiers

SYSKY-2023-1064-01

Identifier Type: -

Identifier Source: org_study_id