Prospective, Single-arm, Phase II Clinical Study of Tirellizumab Combined With Carboplatin and Paclitaxel Polymer Micelles Neoadjuvant Therapy for cN+ Head and Neck Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 85
- 主要终点
- Major pathological response (MPR) rate of metastatic lymph nodes
研究概览
简要总结
To explore the efficiency and safety of Tislelizumab combinated with carboplatin and polymeric micellar paclitaxel as a new neoadjuvant treatment regimen for resectable HNSCC patients with clinical positive lymph node metastasis
详细描述
The 5-year overall survival rate of patients with clinical N-positive head and neck squamous cell carcinoma (HNSCC) is less than 50%, and the clinical outcomes of these patients still need improvement.
Immunotherapy, such as PD-1/PD-L1 inhibitors, has shown excellent efficiency in treating malignant tumors. Anti PD-1 therapy has been approved as a first-line treatment for recurrent/metastatic HNSCC. The results of several phase II clinical trials have shown that neoadjuvant immunotherapy for locally advanced resectable HNSCC has been proven to be safe and feasible. However, immunotherapy has a lower MPR rate for locally advanced HNSCC patients with lymph node metastasis.
Paclitaxel has been used as a first-line induction therapy for locally advanced HNSCC and is an important drug in mediating immunogenic death, enhancing the efficacy of immunotherapy. Previous studies on lung cancer have confirmed that nano-paclitaxel has better induction efficacy than solvent paclitaxel and reduces the rate of distant metastasis.
In summary, the investigators designed this study to explore the efficiency and safety of Tislelizumab combinated with carboplatin and polymeric micellar paclitaxel as a new neoadjuvant treatment regimen for patients with clinical N positive resectable HNSCC, aiming to provide a new treatment option for those patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females ECOG Performance Status 0 or
- •Confirmed pathologic and/or cytologic diagnosis of squamous cell carcinoma of head and neck，T2-4N1-3M0（III-IV）（AJCC 8.0） Histological diagnosis of squamous cell carcinoma of the lip, oral cavity, oropharynx, hypopharynx, larynx.
- •With measurable target lesions by CT or MRI. Adequate bone marrow function. Adequate renal and liver function. Pregnancy test (for patients of childbearing potential) negative at screening. Signed Written Informed Consent.
排除标准
- •Patients who pathologically confirmed non-squamous cell carcinoma Patients who has recurrence or distant metastasis Local lesions have been surgically removed Patients who have received systemic anti-cancer therapy, including hormone therapy Patients who have received treatment targeting PD-1 or PD-L1 Patients with active autoimmune disease or a history of autoimmune disease but may relapse(Patients with the following diseases are not excluded and can be further filtered) Controlled type 1 diabetes Hypothyroidism(If it can be controlled with hormone replacement therapy) Controlled celiac disease Skin diseases that do not require systemic treatment such as Vitiligo, Psoriasis and Hair loss.
- •Any other disease that is not expected to recur without external triggers Any active malignant tumors within 2 years before treatment, except for the specific cancers being studied in this trial and locally recurring cancers that have been cured (such as resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical in situ Cancer or breast cancer) Any disease requiring systemic treatment with corticosteroids (referring to treatment with a dose higher than 10 mg/day of prednisone or equivalent doses of similar drugs) or other immunosuppressive treatments within 14 days before treatment.
- •However, patients who have currently or previously used any of the following steroid regimens can be selected:
- •Adrenaline replacement steroids(Prednisone ≤10mg/day or equivalent dose of similar drugs) Local, ophthalmic, intra-articular, intranasal and inhaled corticosteroids which is Systemic absorbed Minimally Prophylactically short-term (≤7 days) use of corticosteroids (for example, allergy to contrast agents) or for the treatment of non-autoimmune conditions (for example, delayed hypersensitivity reactions caused by contact allergens) Uncontrolled diabetes within 14 days before treatment or laboratory abnormalities with potassium, sodium and corrected calcium levels> 1 after standard drug treatment or hypoalbuminemia grade ≥ 3 History of the following diseases: interstitial lung disease, non-infectious pneumonia or uncontrollable diseases, including pulmonary fibrosis, acute lung disease, etc.
- •Severe chronic or active infection (including tuberculosis infection, etc.) that required systemic antibiotics, antibacterial or antiviral treatment occurred within 14 days before the first administration of the study drug The patient is known to have been infected with HIV Untreated patients with chronic hepatitis B or HBV carriers with chronic hepatitis B virus (HBV) DNA ≥ 500 IU/mL or active hepatitis C virus carriers (HCV) should be excluded.
- •Patients can be selected who is Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B patients (HBV DNA <500 IU/mL) and cured hepatitis C patients.
- •Any surgery requiring general anesthesia has been performed within 28 days before treatment Have had allogeneic stem cell transplantation or organ transplantation
- •Have any of the following cardiovascular risk factors:
- •Cardiogenic chest pain within 28 days before treatment(moderate pain that restricts instrumental activities of daily living) Symptomatic pulmonary embolism within 28 days before treatment Acute myocardial infarction within 6 months before treatment Any history of heart failure that has reached Grade III or IV as defined by the New York Heart Association within 6 months before treatment Grade 2 ventricular arrhythmia within 6 months before the first administration of the study drug Have a history of cerebrovascular accident within 6 months before the first administration of the study drug Have a history of severe hypersensitivity to other monoclonal antibodies Patients with treatment toxicity (caused by previous anti-cancer treatments) have not returned to baseline or stabilized, unless it is an AE that is not considered a possible safety risk (such as hair loss, neuropathy, or specific laboratory abnormalities) History of allergic reactions to cisplatin or other platinum-containing compounds Peripheral nerve disease ≥ Grade 2 defined by NCI CTCAE v5.0 standard Have gotten a live vaccine within 4 weeks before treatment(Seasonal flu vaccines are usually inactivated vaccines and are allowed to be used; The vaccine used in the nasal cavity is a live vaccine and is not allowed to be used) Abuse or dependence on alcohol or drugs and Basic medical conditions (including laboratory abnormalities) that are not conducive to the administration of the study drug , affect the interpretation of drug toxicity or AEs, lead to insufficient compliance with the study execution and possible damage The patient participates in another therapeutic clinical study at the same time
研究组 & 干预措施
treatment group
Neoadjuvant therapy will be performed for a total of 3 cycles, with 21 days as a cycle, which includes: ① Carboplatin: AUC5, weeks 1, 3, and 6, Q3W; ② Polymeric Micellar Paclitaxel: 300mg/m2, weeks 1, 3, and 6, Q3W for three cycles; ③Tirelizumab: 200 mg weeks 1, 3, and 6, Q3W for three cycles; if adjuvant immunotherapy is omitted, Tirelizumab will be administered on weeks 1, 3, 6, 9, 12, 15 after surgery .Participants with clinical N-positive resectable head and neck squamous cell carcinoma for which standard-of-care management would entail definitive surgery followed by adjuvant radiation +/- concurrent chemotherapy are eligible.
干预措施: Carboplatin (Drug)
treatment group
Neoadjuvant therapy will be performed for a total of 3 cycles, with 21 days as a cycle, which includes: ① Carboplatin: AUC5, weeks 1, 3, and 6, Q3W; ② Polymeric Micellar Paclitaxel: 300mg/m2, weeks 1, 3, and 6, Q3W for three cycles; ③Tirelizumab: 200 mg weeks 1, 3, and 6, Q3W for three cycles; if adjuvant immunotherapy is omitted, Tirelizumab will be administered on weeks 1, 3, 6, 9, 12, 15 after surgery .Participants with clinical N-positive resectable head and neck squamous cell carcinoma for which standard-of-care management would entail definitive surgery followed by adjuvant radiation +/- concurrent chemotherapy are eligible.
干预措施: Tislelizumab (Drug)
treatment group
Neoadjuvant therapy will be performed for a total of 3 cycles, with 21 days as a cycle, which includes: ① Carboplatin: AUC5, weeks 1, 3, and 6, Q3W; ② Polymeric Micellar Paclitaxel: 300mg/m2, weeks 1, 3, and 6, Q3W for three cycles; ③Tirelizumab: 200 mg weeks 1, 3, and 6, Q3W for three cycles; if adjuvant immunotherapy is omitted, Tirelizumab will be administered on weeks 1, 3, 6, 9, 12, 15 after surgery .Participants with clinical N-positive resectable head and neck squamous cell carcinoma for which standard-of-care management would entail definitive surgery followed by adjuvant radiation +/- concurrent chemotherapy are eligible.
干预措施: Polymeric Micellar Paclitaxel (Drug)
treatment group
Neoadjuvant therapy will be performed for a total of 3 cycles, with 21 days as a cycle, which includes: ① Carboplatin: AUC5, weeks 1, 3, and 6, Q3W; ② Polymeric Micellar Paclitaxel: 300mg/m2, weeks 1, 3, and 6, Q3W for three cycles; ③Tirelizumab: 200 mg weeks 1, 3, and 6, Q3W for three cycles; if adjuvant immunotherapy is omitted, Tirelizumab will be administered on weeks 1, 3, 6, 9, 12, 15 after surgery .Participants with clinical N-positive resectable head and neck squamous cell carcinoma for which standard-of-care management would entail definitive surgery followed by adjuvant radiation +/- concurrent chemotherapy are eligible.
干预措施: Surgical Resection of Primary +/- Neck Dissection (Procedure)
treatment group
Neoadjuvant therapy will be performed for a total of 3 cycles, with 21 days as a cycle, which includes: ① Carboplatin: AUC5, weeks 1, 3, and 6, Q3W; ② Polymeric Micellar Paclitaxel: 300mg/m2, weeks 1, 3, and 6, Q3W for three cycles; ③Tirelizumab: 200 mg weeks 1, 3, and 6, Q3W for three cycles; if adjuvant immunotherapy is omitted, Tirelizumab will be administered on weeks 1, 3, 6, 9, 12, 15 after surgery .Participants with clinical N-positive resectable head and neck squamous cell carcinoma for which standard-of-care management would entail definitive surgery followed by adjuvant radiation +/- concurrent chemotherapy are eligible.
干预措施: Post-operative radiation therapy (Radiation)
结局指标
主要结局
Major pathological response (MPR) rate of metastatic lymph nodes
时间窗: 10days after surgery
the proportion of cN+ patients with the percentage of residual viable tumor cells in the tumor bed of metastatic lymph nodes less than 10%
次要结局
- pathological downstaging rate(10days after surgery)
- Event-free survival (EFS)(1 years and 3 years)
- Incidence of treatment-related adverse events(from the first day of treatment to 30 days after surgery；if adjuvant immotherapy is omitted, time frame is from the first day of treatment to 30 days after last administration)
- Overall survival（OS）(1 years and 3 years)
- Distant metastasis-free survival(DMFS) rate(1 year and 3 year)
- logical regional-free survival(LRFS) rate(1 year and 3 year)
- Major pathological response (MPR) rate of primary tumor(10days after surgery)
- EORTC QLQ-C30(from 1 week before treatment to 30 days after surgery)