Neoadjuvant Toripalimab and Albumin Paclitaxel /Cisplatin Versus Docetaxel/ Cisplatin/ 5-fluorouracil (TPF) on Pathological Response in Patients With Locally Advanced and Resectable Oral Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Major pathologic response
研究概览
简要总结
To compare the pathological efficacy of neoadjuvant Toripalimab and Albumin paclitaxel /Cisplatin (TTP) with Docetaxel/ Cisplatin/ 5-flurouracil (TPF) for patients with locally advanced resectable oral squamous cell carcinoma (OSCC), and to determine the safety of neoadjuvant TTP. In order to explore a better protocol of neoadjuvant therapy to improve the efficacy in patients with locally advanced OSCC.
详细描述
In the previous "Illuminate" trial, neoadjuvant anti-programmed death-1 (PD-1) of Toripalimab and Albumin paclitaxel /Cisplatin (TTP) therapy was used in 20 patients with locally advanced and resectable oral squamous cell carcinoma (OSCC), and the neoadjuvant therapy was well-tolerated. The major pathologic response (MPR) rate was 60% (12/20), including 30% (6/20) pathological complete response (pCR). Furthermore, the MPR might transfer to survival benefit in the patients received neoadjuvant therapy. Therefore, in this randomized trial, we aimed to compare the pathological response of neoadjuvant TTP therapy versus TPF chemotherapy in the patients with locally advanced OSCC (Illuminate-2 trial). A total of 80 patients will be enrolled in this trial, and the primary endpoint is MPR rate. The neoadjuvant TTP arm will receive two cycles of intravenous Albumin paclitaxel (260mg/ m^2), Cisplatin (75mg/ m^2) and Toripalimab (anti-PD1 inhibitor, 240 mg) on d1 and d22, followed by the standard treatment of surgery and postoperative adjuvant therapy. The neoadjuvant TPF arm will received two cycles of intravenous Docetaxel (75mg/m^2), Cisplatin (75mg/m^2) on d1 (d22), and 5-Fu(750mg/m^2/day) for 5 days (d1-5 and d22-26), followed by the standard treatment of surgery and postoperative adjuvant therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Age: 18-75 years old
- •Gender: male and female
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0-2
- •Histopathological diagnosis of oral squamous cell carcinoma (including tongue, gums, cheek, floor of mouth, hard palate, and posterior molar region)
- •Primary tumor with a clinical stage of III/IVA (T1-2/N1-2/M0 or T3-4a/cN0-2/M0, AJCC2018)
- •Patients must have at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
- •Blood routine: white blood cells (WBCs) >3,000/mm3, hemoglobin >8 g/L, platelets >80,000/mm3
- •Liver function: alanine amino transferase/aspartate amino transferase (ALAT/ASAT) <2.5 times the upper limit of normal and bilirubin <1.5 times the upper limit of normal
- •Renal function: Serum creatinine <1.5 times the upper limit of normal
- •Coagulation function: INR, PT, APTT<1.5 times the upper limit of normal
- •Signed the informed consent form
排除标准
- •Unresolved grade 2 [(Common Terminology Criteria for Adverse Events (CTCAE 5.0)] or higher toxic reactions caused by previous anticancer treatments
- •Known allergic reaction to any ingredients or excipients of the therapy
- •Known history of malignancy, unless been cured and no recurrence for 5 years
- •Known history of radiation to head and neck
- •Active severe clinical infection (> National Cancer Institute (NCI)-CTCAE version 5.0 grade 2 infection)
- •Obvious cardiovascular abnormalities [such as myocardial infarction, superior vena cava syndrome, grade 2 or higher heart disease diagnosed according to the New York Heart Association (NYHA) classification 3 months before enrollment]
- •Patients receiving immunology-based treatment for any reason
- •Patients with a history of active bleeding, coagulopathy, or receiving coumarin anticoagulation therapy
- •Pregnant or lactating women
- •Uncontrollable hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >90 mmHg) or cardiovascular diseases with clinical significance (such as activity), such as cerebrovascular accidents (≤ 6 months before screening), myocardial infarction (≤6 months before screening), unstable angina pectoris, NYHA grade II or above congestive heart failure, or severe arrhythmia that cannot be controlled by drugs or has a potential impact on trial treatment
- •Complicated with severe, uncontrolled infection or known human immunodeficiency virus (HIV) infection, or diagnosed as acquired immunodeficiency syndrome (AIDS); or uncontrolled autoimmune disease; or history of allogeneic tissue/organ transplantation, stem cell or bone marrow transplantation, or solid organ transplantation
- •Participation in other clinical trials within 30 days before enrollment
- •Other situations that the investigator considers unsuitable with respect to participating in the trial
研究组 & 干预措施
Neoadjuvant TTP
The participants will receive two cycles of intravenous Albumin paclitaxel (260mg/ m^2), Cisplatin (75mg/ m^2) and Toripalimab (anti-PD-1 inhibitor, 240 mg) on d1 and d22.
干预措施: Toripalimab (anti-programmed death-1 inhibitor) (Drug)
Neoadjuvant TTP
The participants will receive two cycles of intravenous Albumin paclitaxel (260mg/ m^2), Cisplatin (75mg/ m^2) and Toripalimab (anti-PD-1 inhibitor, 240 mg) on d1 and d22.
干预措施: Albumin paclitaxel (Drug)
Neoadjuvant TTP
The participants will receive two cycles of intravenous Albumin paclitaxel (260mg/ m^2), Cisplatin (75mg/ m^2) and Toripalimab (anti-PD-1 inhibitor, 240 mg) on d1 and d22.
干预措施: Cisplatin (Drug)
Neoadjuvant TPF
The participants will receive two cycles of intravenous Docetaxel (75 mg/m^2) on d1 and d22, Cisplatin (75 mg/m^2) on d1 and d22, and 5-Fluorouracil (750 mg/m^2/day) for 5 days (d1-5 and d22-26), the interval is 16±1 days.
干预措施: Cisplatin (Drug)
Neoadjuvant TPF
The participants will receive two cycles of intravenous Docetaxel (75 mg/m^2) on d1 and d22, Cisplatin (75 mg/m^2) on d1 and d22, and 5-Fluorouracil (750 mg/m^2/day) for 5 days (d1-5 and d22-26), the interval is 16±1 days.
干预措施: Docetaxel (Drug)
Neoadjuvant TPF
The participants will receive two cycles of intravenous Docetaxel (75 mg/m^2) on d1 and d22, Cisplatin (75 mg/m^2) on d1 and d22, and 5-Fluorouracil (750 mg/m^2/day) for 5 days (d1-5 and d22-26), the interval is 16±1 days.
干预措施: 5-Fluorouracil (Drug)
结局指标
主要结局
Major pathologic response
时间窗: 3 months
The major pathologic response (MPR): the percentage of tumor cells before and after treatment was compared according to biopsy specimens before neoadjuvant therapy and pathological specimens after surgery; the percentage of residual viable tumor (RVT) cells was evaluated on resected tumor slides. MPR was defined as ≤ 10% RVT%.
次要结局
- 2-year disease-free survival rate(24 months)
- 2-year overall survival rate(24 months)
研究者
Lai-ping Zhong
Professor
Shanghai Jiao Tong University School of Medicine