EFFECT-neo: A Prospective, Open-label, Multicenter Phase III Study to Evaluate Efficacy and Safety of Pembrolizumab Combined With Standard Chemotherapy in the Neoadjuvant Treatment of Local Advanced (LA) HNSCC
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 272
- 试验地点
- 1
- 主要终点
- Pathological complete response rate (pCR) of pembrolizumab combined with standard chemotherapy neoadjuvant therapy in patients with locally advanced head and neck squamous cell carcinoma
研究概览
简要总结
This study is a prospective, open-label, multi-center phase III study; patients with untreated stage IIIA to stage IVB head and neck squamous cell carcinoma (including oral cavity cancer, oropharyngeal cancer, hypopharyngeal cancer, and laryngeal cancer) who meet the inclusion criteria are randomized 1:1 and given pembrolizumab 200 mg d1+ chemotherapy for 2 cycles (experimental group), 2 cycles of chemotherapy (control group), and then stratified according to the patient's condition. If the imaging evaluation after neoadjuvant treatment is (complete response, CR), adjuvant radiotherapy will be given; if the imaging evaluation is (partial response, PR) or (stable disease, SD), surgery (within 2 weeks) will be performed, followed by standard treatment. The main research hypothesis of this study: pembrolizumab combined with standard chemotherapy can significantly improve the rate of pathological complete response (pCR) compared with standard chemotherapy.
详细描述
This study is a prospective, open-label, multi-center phase III study; Patients with untreated stage IIIA to stage IVB head and neck squamous cell carcinoma (including oral cavity cancer, oropharyngeal cancer, hypopharyngeal cancer, and laryngeal cancer) who met the inclusion criteria were randomized in a 1:1 ratio and given 2 cycles of pembrolizumab 200 mg d1 + chemotherapy (see the table below for detailed chemotherapy regimens) (experimental group) and 2 cycles of chemotherapy (control group), and were divided according to the patient's condition. layer. If the imaging evaluation is CR after neoadjuvant treatment, radiotherapy (60-70Gy) ± chemotherapy (investigator's choice) will be given as adjuvant treatment; if the imaging evaluation is PR or SD, surgery (within 2 weeks) will be performed, and then standard treatment will be given. treat. If the imaging evaluation is PD, standard treatment will be given. Enrolled patients must closely monitor the adverse reactions of chemotherapy and record the time, grade, treatment measures, outcomes, etc. All patients were reviewed every 3 months for 1 year; after 1 year, they were reviewed every 6 months for 3 years; patient recurrence and survival data were recorded.
The investigators speculate that, compared with the traditional induction chemotherapy regimen, the induction chemotherapy regimen of pembrolizumab combined with chemotherapy may be safer and more effective, and easier for clinical application. At present, there are no research reports on the induction chemotherapy of pembrolizumab combined with cisplatin and nab-paclitaxel for patients with locally advanced operable head and neck squamous cell carcinoma. We intend to conduct a randomized controlled study on the efficacy and safety of pembrolizumab combined with chemotherapy as neoadjuvant therapy in Chinese patients with operable head and neck squamous cell carcinoma, and provide a basis for the neoadjuvant therapy of pembrolizumab combined with chemotherapy.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with stage IIIA-IVB head and neck squamous cell carcinoma confirmed by histology and/or cytology;
- •Have not received immunotherapy in the past;
- •The researchers believe that he can safely receive pembrolizumab combined with chemotherapy or neoadjuvant chemotherapy;
- •Age ≥18 years;
- •Measurable disease as defined by RECIST v1.1;
- •Organs function normally;
- •Female and male participants of reproductive potential must agree to use appropriate contraception throughout the study period and for 180 days after the last study treatment;
- •Male participants must not donate sperm throughout the study and for 180 days after the last study treatment.
排除标准
- •Presence of distant metastasis;
- •Female subjects with a positive urine pregnancy test within 72 hours before the start of the study or within 24 hours after starting radiation therapy (with or without cisplatin);
- •received a live vaccine within 30 days before enrollment;
- •Diagnosed with immunodeficiency or receiving systemic steroid treatment or any other form of immunosuppressive treatment within 7 days before enrollment;
- •Have imaging detectable (even if asymptomatic and/or previously treated) central nervous system metastases and/or cancerous meningitis;
- •Have undergone surgery before commencing the study or have failed to recover adequately from toxicity or complications resulting from the intervention;
- •Previous allogeneic tissue/solid organ transplant;
- •Severe hypersensitivity reaction (≥Grade 3) to pembrolizumab or any of its excipients, radiotherapy, platinum, paclitaxel, 5-FU or their analogs;
- •Have an active autoimmune disease requiring systemic therapy in the past 2 years;
- •History of (non-infectious) pneumonia requiring steroid treatment;
- •Have a history of human immunodeficiency virus (HIV) infection;
- •Have a history of hepatitis B or be positive for hepatitis B virus (defined as a positive reaction to hepatitis B surface antigen [HBsAg]) or active hepatitis C (defined as detection of hepatitis C virus [HCV] ribonucleic acid).
- •Have any medical history, treatment, or laboratory abnormalities that could confound the study results, interfere with participant participation throughout the study, or be detrimental to the best interests of the participant (e.g., Hashimoto's thyroiditis, etc.);
- •Have a known history of mental illness or substance abuse disorder
研究组 & 干预措施
Pembrolizumab combined with standard chemotherapy
Patients receive pembrolizumab 200mg, IV, on day1 of Q3W; plus platinum (cisplatin 75 mg/m^2, IV, day 1 of Q3W or carboplatin AUC (area under curve) 2, IV, day 1-3 of Q3W or nedaplatin 80-100 mg/m^2, IV, day 2-4 of Q3W); plus other chemotherapy（nab-paclitaxel 260 mg/m^2, IV, day 1 of Q3W or docetaxel 75 mg/m^2, IV, day 1 of Q3W or liposomal paclitaxel 135-175 mg/m^2, IV, day 1 of Q3W or fluorouracil 750 mg/m^2, IV, day 1-5 of Q3W）; total 2 cycle
干预措施: Nab paclitaxel (Drug)
Pembrolizumab combined with standard chemotherapy
Patients receive pembrolizumab 200mg, IV, on day1 of Q3W; plus platinum (cisplatin 75 mg/m^2, IV, day 1 of Q3W or carboplatin AUC (area under curve) 2, IV, day 1-3 of Q3W or nedaplatin 80-100 mg/m^2, IV, day 2-4 of Q3W); plus other chemotherapy（nab-paclitaxel 260 mg/m^2, IV, day 1 of Q3W or docetaxel 75 mg/m^2, IV, day 1 of Q3W or liposomal paclitaxel 135-175 mg/m^2, IV, day 1 of Q3W or fluorouracil 750 mg/m^2, IV, day 1-5 of Q3W）; total 2 cycle
干预措施: Pembrolizumab (Drug)
Pembrolizumab combined with standard chemotherapy
Patients receive pembrolizumab 200mg, IV, on day1 of Q3W; plus platinum (cisplatin 75 mg/m^2, IV, day 1 of Q3W or carboplatin AUC (area under curve) 2, IV, day 1-3 of Q3W or nedaplatin 80-100 mg/m^2, IV, day 2-4 of Q3W); plus other chemotherapy（nab-paclitaxel 260 mg/m^2, IV, day 1 of Q3W or docetaxel 75 mg/m^2, IV, day 1 of Q3W or liposomal paclitaxel 135-175 mg/m^2, IV, day 1 of Q3W or fluorouracil 750 mg/m^2, IV, day 1-5 of Q3W）; total 2 cycle
干预措施: Cisplatin (Drug)
Pembrolizumab combined with standard chemotherapy
Patients receive pembrolizumab 200mg, IV, on day1 of Q3W; plus platinum (cisplatin 75 mg/m^2, IV, day 1 of Q3W or carboplatin AUC (area under curve) 2, IV, day 1-3 of Q3W or nedaplatin 80-100 mg/m^2, IV, day 2-4 of Q3W); plus other chemotherapy（nab-paclitaxel 260 mg/m^2, IV, day 1 of Q3W or docetaxel 75 mg/m^2, IV, day 1 of Q3W or liposomal paclitaxel 135-175 mg/m^2, IV, day 1 of Q3W or fluorouracil 750 mg/m^2, IV, day 1-5 of Q3W）; total 2 cycle
干预措施: Carboplatin (Drug)
Pembrolizumab combined with standard chemotherapy
Patients receive pembrolizumab 200mg, IV, on day1 of Q3W; plus platinum (cisplatin 75 mg/m^2, IV, day 1 of Q3W or carboplatin AUC (area under curve) 2, IV, day 1-3 of Q3W or nedaplatin 80-100 mg/m^2, IV, day 2-4 of Q3W); plus other chemotherapy（nab-paclitaxel 260 mg/m^2, IV, day 1 of Q3W or docetaxel 75 mg/m^2, IV, day 1 of Q3W or liposomal paclitaxel 135-175 mg/m^2, IV, day 1 of Q3W or fluorouracil 750 mg/m^2, IV, day 1-5 of Q3W）; total 2 cycle
干预措施: Nedaplatin (Drug)
Pembrolizumab combined with standard chemotherapy
Patients receive pembrolizumab 200mg, IV, on day1 of Q3W; plus platinum (cisplatin 75 mg/m^2, IV, day 1 of Q3W or carboplatin AUC (area under curve) 2, IV, day 1-3 of Q3W or nedaplatin 80-100 mg/m^2, IV, day 2-4 of Q3W); plus other chemotherapy（nab-paclitaxel 260 mg/m^2, IV, day 1 of Q3W or docetaxel 75 mg/m^2, IV, day 1 of Q3W or liposomal paclitaxel 135-175 mg/m^2, IV, day 1 of Q3W or fluorouracil 750 mg/m^2, IV, day 1-5 of Q3W）; total 2 cycle
干预措施: Docetaxel (Drug)
Pembrolizumab combined with standard chemotherapy
Patients receive pembrolizumab 200mg, IV, on day1 of Q3W; plus platinum (cisplatin 75 mg/m^2, IV, day 1 of Q3W or carboplatin AUC (area under curve) 2, IV, day 1-3 of Q3W or nedaplatin 80-100 mg/m^2, IV, day 2-4 of Q3W); plus other chemotherapy（nab-paclitaxel 260 mg/m^2, IV, day 1 of Q3W or docetaxel 75 mg/m^2, IV, day 1 of Q3W or liposomal paclitaxel 135-175 mg/m^2, IV, day 1 of Q3W or fluorouracil 750 mg/m^2, IV, day 1-5 of Q3W）; total 2 cycle
干预措施: Liposomal paclitaxel (Drug)
Pembrolizumab combined with standard chemotherapy
Patients receive pembrolizumab 200mg, IV, on day1 of Q3W; plus platinum (cisplatin 75 mg/m^2, IV, day 1 of Q3W or carboplatin AUC (area under curve) 2, IV, day 1-3 of Q3W or nedaplatin 80-100 mg/m^2, IV, day 2-4 of Q3W); plus other chemotherapy（nab-paclitaxel 260 mg/m^2, IV, day 1 of Q3W or docetaxel 75 mg/m^2, IV, day 1 of Q3W or liposomal paclitaxel 135-175 mg/m^2, IV, day 1 of Q3W or fluorouracil 750 mg/m^2, IV, day 1-5 of Q3W）; total 2 cycle
干预措施: Fluorouracil (Drug)
Standard chemotherapy
Patients receive platinum (cisplatin 75 mg/m^2, IV, day 1 of Q3W or carboplatin AUC (area under curve) 2, IV, day 1-3 of Q3W or nedaplatin 80-100 mg/m^2, IV, day 2-4 of Q3W); plus other chemotherapy（nab-paclitaxel 260 mg/m^2, IV, day 1 of Q3W or docetaxel 75 mg/m^2, IV, day 1 of Q3W or liposomal paclitaxel 135-175 mg/m^2, IV, day 1 of Q3W or fluorouracil 750 mg/m^2, IV, day 1-5 of Q3W）; total 2 cycle
干预措施: Cisplatin (Drug)
Standard chemotherapy
Patients receive platinum (cisplatin 75 mg/m^2, IV, day 1 of Q3W or carboplatin AUC (area under curve) 2, IV, day 1-3 of Q3W or nedaplatin 80-100 mg/m^2, IV, day 2-4 of Q3W); plus other chemotherapy（nab-paclitaxel 260 mg/m^2, IV, day 1 of Q3W or docetaxel 75 mg/m^2, IV, day 1 of Q3W or liposomal paclitaxel 135-175 mg/m^2, IV, day 1 of Q3W or fluorouracil 750 mg/m^2, IV, day 1-5 of Q3W）; total 2 cycle
干预措施: Carboplatin (Drug)
Standard chemotherapy
Patients receive platinum (cisplatin 75 mg/m^2, IV, day 1 of Q3W or carboplatin AUC (area under curve) 2, IV, day 1-3 of Q3W or nedaplatin 80-100 mg/m^2, IV, day 2-4 of Q3W); plus other chemotherapy（nab-paclitaxel 260 mg/m^2, IV, day 1 of Q3W or docetaxel 75 mg/m^2, IV, day 1 of Q3W or liposomal paclitaxel 135-175 mg/m^2, IV, day 1 of Q3W or fluorouracil 750 mg/m^2, IV, day 1-5 of Q3W）; total 2 cycle
干预措施: Nedaplatin (Drug)
Standard chemotherapy
Patients receive platinum (cisplatin 75 mg/m^2, IV, day 1 of Q3W or carboplatin AUC (area under curve) 2, IV, day 1-3 of Q3W or nedaplatin 80-100 mg/m^2, IV, day 2-4 of Q3W); plus other chemotherapy（nab-paclitaxel 260 mg/m^2, IV, day 1 of Q3W or docetaxel 75 mg/m^2, IV, day 1 of Q3W or liposomal paclitaxel 135-175 mg/m^2, IV, day 1 of Q3W or fluorouracil 750 mg/m^2, IV, day 1-5 of Q3W）; total 2 cycle
干预措施: Nab paclitaxel (Drug)
Standard chemotherapy
Patients receive platinum (cisplatin 75 mg/m^2, IV, day 1 of Q3W or carboplatin AUC (area under curve) 2, IV, day 1-3 of Q3W or nedaplatin 80-100 mg/m^2, IV, day 2-4 of Q3W); plus other chemotherapy（nab-paclitaxel 260 mg/m^2, IV, day 1 of Q3W or docetaxel 75 mg/m^2, IV, day 1 of Q3W or liposomal paclitaxel 135-175 mg/m^2, IV, day 1 of Q3W or fluorouracil 750 mg/m^2, IV, day 1-5 of Q3W）; total 2 cycle
干预措施: Docetaxel (Drug)
Standard chemotherapy
Patients receive platinum (cisplatin 75 mg/m^2, IV, day 1 of Q3W or carboplatin AUC (area under curve) 2, IV, day 1-3 of Q3W or nedaplatin 80-100 mg/m^2, IV, day 2-4 of Q3W); plus other chemotherapy（nab-paclitaxel 260 mg/m^2, IV, day 1 of Q3W or docetaxel 75 mg/m^2, IV, day 1 of Q3W or liposomal paclitaxel 135-175 mg/m^2, IV, day 1 of Q3W or fluorouracil 750 mg/m^2, IV, day 1-5 of Q3W）; total 2 cycle
干预措施: Liposomal paclitaxel (Drug)
Standard chemotherapy
Patients receive platinum (cisplatin 75 mg/m^2, IV, day 1 of Q3W or carboplatin AUC (area under curve) 2, IV, day 1-3 of Q3W or nedaplatin 80-100 mg/m^2, IV, day 2-4 of Q3W); plus other chemotherapy（nab-paclitaxel 260 mg/m^2, IV, day 1 of Q3W or docetaxel 75 mg/m^2, IV, day 1 of Q3W or liposomal paclitaxel 135-175 mg/m^2, IV, day 1 of Q3W or fluorouracil 750 mg/m^2, IV, day 1-5 of Q3W）; total 2 cycle
干预措施: Fluorouracil (Drug)
结局指标
主要结局
Pathological complete response rate (pCR) of pembrolizumab combined with standard chemotherapy neoadjuvant therapy in patients with locally advanced head and neck squamous cell carcinoma
时间窗: 12 week
pCR was defined as the absence of residual invasive squamous cell carcinoma within the primary tumor specimen on resection/needle biopsy
Pathological complete response rate (pCR) of standard chemotherapy neoadjuvant chemotherapy in patients with locally advanced head and neck squamous cell carcinoma
时间窗: 12 week
pCR was defined as the absence of residual invasive squamous cell carcinoma within the primary tumor specimen on resection/needle biopsy
次要结局
- The objective response rate (ORR) of neoadjuvant therapy with pembrolizumab combined with standard chemotherapy(12 week)
- The objective response rate (ORR) of neoadjuvant chemotherapy with standard chemotherapy(6 week)
- The 1-year and 2-year event-free survival rates (1y-EFS, 2y-EFS) after pembrolizumab combined with standard chemotherapy neoadjuvant therapy(2 year)
- Pathological complete response rate (pCR) of pembrolizumab combined with standard chemotherapy as neoadjuvant therapy in patients of locally advanced head and neck squamous cell carcinoma with CPS (combined positive score) <1(12 week)
- The 1-year and 2-year event-free survival rate (1y-EFS, 2y-EFS) after neoadjuvant chemotherapy with standard chemotherapy(2 year)
- The functional preservation rate of pembrolizumab combined with standard chemotherapy(3 year)
- The functional preservation rate of standard chemotherapy(3 year)
- The 2-year overall survival rate (2y-OS) after Neoadjuvant pembrolizumab combined with standard chemotherapy(2 year)
- The 2-year overall survival rate (2y-OS) after Neoadjuvant Therapy with standard chemotherapy(2 year)
- Pathological complete response rate (pCR) of pembrolizumab combined with standard chemotherapy as neoadjuvant therapy in patients of locally advanced head and neck squamous cell carcinoma with CPS (combined positive score) ≥1(12 week)
- The 2-year event-free survival rates (2y-EFS) after pembrolizumab combined with standard chemotherapy neoadjuvant therapy with CPS (combined positive score) <1(2 year)
- The 2-year event-free survival rates (2y-EFS) after pembrolizumab combined with standard chemotherapy neoadjuvant therapy with CPS (combined positive score) ≥1(2 year)
- The 2-year overall survival rate (2y-OS) after Neoadjuvant pembrolizumab combined with standard chemotherapy with CPS(combined positive score) ≥1(2 year)
- The 2-year overall survival rate (2y-OS) after Neoadjuvant pembrolizumab combined with standard chemotherapy with CPS(combined positive score) <1(2 year)
- Incidence of Treatment-Emergent Adverse Events (TRAEs) of pembrolizumab combined with standard chemotherapy in neoadjuvant therapy(3 year)
- Incidence of Treatment-Emergent Adverse Events (TRAEs) of neoadjuvant chemotherapy with standard chemotherapy(3 year)
- The quality of life of pembrolizumab combined with standard chemotherapy neoadjuvant therapy measured by KPS (Karnofsky performance status) scores(3 year)
- The quality of life of standard chemotherapy neoadjuvant therapy measured by KPS (Karnofsky performance status) scores(3 year)