Induction Therapy With Nab-paclitaxel, Cisplatin and Pembrolizumab in Untreated Locally Advanced Head and Neck Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 86
- 试验地点
- 1
- 主要终点
- Rate of organ preservation
研究概览
简要总结
To study induction therapy with Nab-paclitaxel, Cisplatin and Pembrolizumab in patients with Locally Advanced HNSCC.
详细描述
This study is a non-randomized, single-arm, single-institutional phase II study including patients with Locally Advanced Head and Neck Squamous Cell Carcinoma eligible for resection. Nab-paclitaxel (260 mg/m² IV), cisplatin (75 mg/m² IV), and Pembrolizumab (200 mg IV) will be administered for two cycles of three weeks duration each. Surgery or CRT will be performed after induction therapy. Patients with PR and maximum tumor diameter ≤ 3cm or CR evaluated by MDT after 2 courses induction therapy can receive CRT. Evaluation was performed 3 months after CRT. After MDT discussion, patients with high-risk factors need maintenance treatment. Patients with PR but the maximum diameter of tumor > 3cm or SD or PD can receive surgery directly. After surgery, adjuvant CRT will be given for patients with high-risk factors. Objective response rate, safety, and rate of organ preservation will be the primary outcome measures.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed Head and Neck Squamous Cell Carcinoma (oral cavity, oropharynx, laryngeal and hypopharynx) with locoregionally-advanced disease stage III or IVA without metastasis , previously untreated (AJCC 8th) and had at least one tumour lesion measurable per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- •Measurable disease based on RECIST 1.1
- •ECOG performance status 0-1
- •Men and women, Age ≥18 and ≤ 70 years at the time of signing informed consent,
- •Adequate hepatic, cardiac and renal function as demonstrated by 1) Hematology: ANC≥1.5×10^9 /L, HGB≥9 g/dL, PLT≥80×10^9 /L; 2) Renal: Serum creatinine < 1.5x ULN or CrCl > 60mL/min; 3) Hepatic: Total Bilirubin ≤ 1.5 x ULN, AST/ALT ≤ 2.5 x ULN and ALP≤5 x ULN.
- •Female subjects of childbearing potential should have a negative pregnancy test result within 28 days prior to enrollment. If the result is more than 7 days before receiving the first dose of study medication, a urine pregnancy test is required for verification.
- •Voluntary informed consent, joining the study with good compliance
排除标准
- •Active, known, or suspected autoimmune disease or Type I diabetes or hypothyroidism requiring hormone replacement therapy and skin diseases requiring systemic treatment.
- •currently received systemic steroid therapy with dose superior to 10 mg/day of prednisone or equivalent or any other form of immunosuppressive therapy within 14 days prior to the enrollment
- •Has known active Hepatitis B (e.g., HBsAg reactive and HBV DNA≥1×10^4 copies /mL) or Hepatitis C or HIV
- •Active pulmonary tuberculosis (TB) infection was judged according to chest X-ray examination/CT, sputum examination and clinical physical examination.
- •Patients with severe heart disease include congestive heart failure, uncontrollable high-risk arrhythmias, unstable angina pectoris, myocardial infarction, and intractable hypertension.
- •Pregnant or breastfeeding women.
- •The patient (male or female) has the possibility of fertility, but is unwilling or does not take effective contraceptive measures.
- •Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device
- •Has had another known invasive malignancy or unresectable cancer.
- •Received a live vaccine within 30 days of planned start of study therapy.
- •History or current evidence of any condition, therapy, or laboratory abnormality that might influence the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
研究组 & 干预措施
Experimental
All enrolled patients will receive two cycles of chemotherapy consisting of nab-paclitaxel (260 mg/m² on days 1), cisplatin (75 mg/m² on days 1), and Pembrolizumab (200 mg on days 1). Each cycle is repeated every 21 days.
After induction therapy, patients with PR but the maximum diameter of tumor > 3cm or SD or PD can receive surgery directly. After surgery, adjuvant CRT will be given for patients with high-risk factors.
After induction therapy, patients with PR and maximum tumor diameter ≤ 3cm or CR evaluated by MDT after 2 courses induction therapy can receive CRT. Evaluation was performed 3 months after CRT. After MDT discussion, patients with high-risk factors need maintenance treatment.
干预措施: Nab-paclitaxel, cisplatin and Pembrolizumab combination (Drug)
Experimental
All enrolled patients will receive two cycles of chemotherapy consisting of nab-paclitaxel (260 mg/m² on days 1), cisplatin (75 mg/m² on days 1), and Pembrolizumab (200 mg on days 1). Each cycle is repeated every 21 days.
After induction therapy, patients with PR but the maximum diameter of tumor > 3cm or SD or PD can receive surgery directly. After surgery, adjuvant CRT will be given for patients with high-risk factors.
After induction therapy, patients with PR and maximum tumor diameter ≤ 3cm or CR evaluated by MDT after 2 courses induction therapy can receive CRT. Evaluation was performed 3 months after CRT. After MDT discussion, patients with high-risk factors need maintenance treatment.
干预措施: surgery (Procedure)
Experimental
All enrolled patients will receive two cycles of chemotherapy consisting of nab-paclitaxel (260 mg/m² on days 1), cisplatin (75 mg/m² on days 1), and Pembrolizumab (200 mg on days 1). Each cycle is repeated every 21 days.
After induction therapy, patients with PR but the maximum diameter of tumor > 3cm or SD or PD can receive surgery directly. After surgery, adjuvant CRT will be given for patients with high-risk factors.
After induction therapy, patients with PR and maximum tumor diameter ≤ 3cm or CR evaluated by MDT after 2 courses induction therapy can receive CRT. Evaluation was performed 3 months after CRT. After MDT discussion, patients with high-risk factors need maintenance treatment.
干预措施: Adjuvant Chemoradiotherapy (Radiation)
Experimental
All enrolled patients will receive two cycles of chemotherapy consisting of nab-paclitaxel (260 mg/m² on days 1), cisplatin (75 mg/m² on days 1), and Pembrolizumab (200 mg on days 1). Each cycle is repeated every 21 days.
After induction therapy, patients with PR but the maximum diameter of tumor > 3cm or SD or PD can receive surgery directly. After surgery, adjuvant CRT will be given for patients with high-risk factors.
After induction therapy, patients with PR and maximum tumor diameter ≤ 3cm or CR evaluated by MDT after 2 courses induction therapy can receive CRT. Evaluation was performed 3 months after CRT. After MDT discussion, patients with high-risk factors need maintenance treatment.
干预措施: Radical concurrent chemoradiotherapy (Drug)
结局指标
主要结局
Rate of organ preservation
时间窗: 24 months
After two courses of induction treatment, MDT discussed whether to accept surgical treatment or concurrent chemoradiotherapy, and the proportion of patients whose organ function can be preserved after treatment.
Evaluation of Safety
时间窗: 24 months
Toxicity will be evaluated according to NCI-CTCAE v4.03
Objective response rate
时间窗: 24 months
Objective response rate (ORR) will be determinated by evaluation of Complete Response (CR) and Partial Response (PR)
次要结局
- overall survival (OS)(24 months)
- progression-free survival (PFS)(24 months)
研究者
MA HAIQING
chief physician
Guangdong Provincial People's Hospital