Neoadjuvant Chemotherapy, Tislelizumab With Afatinib for the Treatment of Resectable Head and Neck Squamous Cell Carcinoma: A Single-Arm Phase 2 Trial (neoCHANCE-2 Trial)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Pathologic Complete Response
研究概览
简要总结
To explore the efficiency and safety of TP chemotherapy, tislelizumab, combined with afatinib as a new neoadjuvant treatment regimen for patients with resectable HNSCC.
详细描述
More than 60% of patients with Head and neck squamous cell carcinoma (HNSCC) have locally advanced or metastatic disease at the time of diagnosis, with a 5-year overall survival rate of less than 60%. The clinical outcomes of those patients still need to be improved.
Neoadjuvant therapy theoretically could reduce tumor volume, increase organ retention rate, and improve clinical prognosis. However, results from several phase III clinical trials have not proved a significant survival benefit of neoadjuvant chemotherapy for patients with resectable HNSCC except for nasopharyngeal carcinoma. There is an urgent need to explore new neoadjuvant treatment options for those patients.
Immunotherapy such as PD-1/PD-L1 inhibitors have shown excellent efficiency in the treatment of malignancies. Anti-PD-1 therapy is approved as the first-line treatment of recurrent/metastatic HNSCC. Neoadjuvant immunotherapy for the treatment of locally advanced and resectable HNSCC has been demonstrated to be feasible in some trials.
Afatinib, as an irreversible ErbB tyrosine kinase inhibitor (TKI), has been used as the second-line treatment for recurrent and/or metastatic HNSCC. A previous study published in 2018 confirmed that afatinib can be administered safely before surgery.
In summary, we designed this study to explore the efficiency and safety of chemotherapy (TP regimen), anti-PD1 immunotherapy (tislelizumab), combined with EGFR-TKI (afatinib) as a new neoadjuvant treatment regimen for patients with 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or above.
- •Patients with pathologically confirmed HNSCC (except for nasopharyngeal carcinoma) and meet the following conditions:
- •were newly diagnosed and without distant metastasis;
- •were deemed surgically resectable evaluated by a head and neck surgeon;
- •were willing to undergo surgery.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Adequate organ and bone marrow function:
- •absolute neutrophil count ≥ 1.5 × 10^9/L, hemoglobin ≥ 80 g/L, platelets ≥ 80 × 10^9/L;
- •ALT, AST and ALP < 2.5× upper limit of normal (ULN), total bilirubin ≤ 2×ULN;
- •albumin≥ 2.8 g/dL；
- •creatinine clearance ≥ 60 ml/min；
- •INR≤ 1.5；APTT≤ 1.5×ULN；
- •Written informed consent.
排除标准
- •History of other malignancies (except for the history of malignant tumors that have been cured and have not recurred within 5 years, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, in situ cervical cancer, and gastrointestinal mucosal cancer, etc.）
- •Have an active autoimmune disease requiring systemic treatment or a documented history of clinically severe autoimmune disease.
- •Any history of allergic disease, or a sever hypersensitivity reaction to drugs, or allergy to the study drug components.
- •Any of prior therapy with:
- •anti-PD-1, anti-PD-L1/2, anti-CTLA-4 antibody, anti-EGFR antibody or EGFR-TKIs；
- •antitumor vaccine;
- •any active vaccine against an infectious disease within 4 weeks prior to the first dose or planned during the study period;
- •major surgery or serious trauma within 4 weeks before the first dose;
- •toxicity from prior antitumor therapy has not recovered to ≤ CTCAE Version 5.0 Grade 1 or the level specified by the inclusion/exclusion criteria.
- •With serious medical diseases, such as grade II and above cardiac dysfunction (NYHA criteria), ischemic heart disease, supraventricular or ventricular arrhythmia, poorly controlled diabetes mellitus, poorly controlled hypertension, echocardiographic ejection fraction < 50%, etc.
- •With interstitial pneumonitis, non-infectious pneumonitis, active pulmonary tuberculosis, or history of pulmonary tuberculosis infection that were not controlled by treatment.
- •With hyperthyroidism, or organic thyroid disease.
- •With active infection, or unexplained fever during the screening period or 48 hours before the first dose.
- •With active hepatitis B or C, or known history of positive HIV test, or acquired immunodeficiency syndrome.
- •History of a clear neurological or psychiatric disorder.
- •History of drug abuse or alcohol abuse.
- •Women who are pregnant or breastfeeding, or have a reproductive plan from the screening period to 3 months after the end of the study, or have sex without contraceptive measures, or are unwilling to take appropriate contraceptive measures.
- •Received any investigational drug within 4 weeks prior to the first dose, or concurrently enrolled in another clinical trial.
- •Any other factors that are not suitable for inclusion in this study judged by investigators.
研究组 & 干预措施
Treatment Cohort
Participants will receive
- TP chemotherapy every 3 weeks x 2 cycles (Nab-paclitaxel 260mg/m^2 IV on day1, Cisplatin 75mg/m^2 IV on day 1);
- Tislelizumab 200mg IV every 3 weeks x 2 cycles;
- Afatinib 30mg PO everyday x 6 weeks.
干预措施: Nab-paclitaxel (Drug)
Treatment Cohort
Participants will receive
- TP chemotherapy every 3 weeks x 2 cycles (Nab-paclitaxel 260mg/m^2 IV on day1, Cisplatin 75mg/m^2 IV on day 1);
- Tislelizumab 200mg IV every 3 weeks x 2 cycles;
- Afatinib 30mg PO everyday x 6 weeks.
干预措施: Cisplatin (Drug)
Treatment Cohort
Participants will receive
- TP chemotherapy every 3 weeks x 2 cycles (Nab-paclitaxel 260mg/m^2 IV on day1, Cisplatin 75mg/m^2 IV on day 1);
- Tislelizumab 200mg IV every 3 weeks x 2 cycles;
- Afatinib 30mg PO everyday x 6 weeks.
干预措施: Tislelizumab (Biological)
Treatment Cohort
Participants will receive
- TP chemotherapy every 3 weeks x 2 cycles (Nab-paclitaxel 260mg/m^2 IV on day1, Cisplatin 75mg/m^2 IV on day 1);
- Tislelizumab 200mg IV every 3 weeks x 2 cycles;
- Afatinib 30mg PO everyday x 6 weeks.
干预措施: Afatinib (Drug)
结局指标
主要结局
Pathologic Complete Response
时间窗: Time of surgery
Pathologic complete response was defined as the absence of viable tumor cells.
次要结局
- Major Pathologic Response(Time of surgery)
- Objective Response Rate(Up to 8 weeks)
- Adverse Events(Up to 12 weeks)
- Disease-free Survival(1 year)
- Overall Survival(1 year)
研究者
Xingchen Peng
Professor
West China Hospital