A Prospective Randomized Controlled Trial Comparing Low-Dose Radiotherapy Combined With Targeted Therapy and Immunotherapy Versus Targeted Therapy and Immunotherapy Alone as Neoadjuvant Therapy in Patients With Operable Head and Neck Squamous Cell Carcinoma.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 98
- 试验地点
- 1
- 主要终点
- Major Pathologic Response
研究概览
简要总结
This study aimed to compare the efficacy of neoadjuvant low-dose radiotherapy combined with targeted therapy and immunotherapy versus targeted therapy and immunotherapy alone in patients with resectable head and neck squamous cell carcinoma.
详细描述
Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumor in the world. Due to its special anatomical location, HNSCC affects patients' appearance and physiological functions. Comprehensive treatments such as surgery, radiotherapy, and chemotherapy are often adopted. More than 60% of patients are diagnosed with locally advanced or metastatic diseases, resulting in a low 5-year survival rate. Locally advanced patients have high recurrence and metastasis rates and a poor prognosis. Neoadjuvant therapy before surgery theoretically can improve the possibility of radical surgery and the organ preservation rate. However, except for nasopharyngeal carcinoma, induction chemotherapy has not brought significant survival benefits to HNSCC patients, and new treatment regimens are urgently needed.
EGFR is overexpressed in 90% of HNSCC patients. The PD-1/PD-L1 signaling pathway is an important mechanism of tumor escape. Anti-PD-1/PD-L1 monoclonal antibodies have shown good efficacy and high safety in the treatment of malignant tumors. The combination of radiotherapy and immunotherapy can induce an anti-tumor immune response. Low-dose radiotherapy has low toxicity and can reprogram the tumor immune microenvironment. Multiple studies have confirmed the safety and feasibility of its combination with immunotherapy.
The previously conducted "Prospective, Single-arm Clinical Study of Low-dose Radiotherapy Plus Tislelizumab Combined with Afatinib for Neoadjuvant Therapy of Resectable Head and Neck Squamous Cell Carcinoma" has demonstrated good safety and efficacy. Based on this, a head-to-head clinical study is planned to compare the efficacy of low-dose radiotherapy combined with targeted therapy and immunotherapy and pure targeted therapy and immunotherapy in patients with resectable HNSCC, explore the clinical benefits of this new treatment measure, and provide new treatment options for HNSCC patients.
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
- •Age 18 years or above.
- •Patients with pathologically confirmed HNSCC (except for nasopharyngeal carcinoma) and meet the following condition:
- •①Were newly diagnosed and without distant metastasis; were deemed surgically resectable, evaluated by a head and neck surgeon;
- •②Were willing to undergo surgery;
- •③Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
- •④Adequate 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 severe hypersensitivity reaction to drugs, or allergy to the study drug components.
- •Any of prior therapy with:
- •①anti-PD-1, anti-PD-L1/2, anti-CTLA-4 antibody, anti-EGFR antibody or EGFR-TKIs； ②antitumor vaccine; ③any active vaccine against an infectious disease within 4 weeks before the first dose or planned during the study period; ④major surgery or serious trauma within 4 weeks before the first dose; ⑤toxicity 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
Low-dose radiotherapy + Immunotherapy + Targeted therapy
- Tislelizumab administration on days 1 and 22, and afatinib continuous administration from days 1 to 42.
- Low-dose radiotherapy, 4Gy/2f.
- Surgery.
干预措施: Afatinib (Drug)
Low-dose radiotherapy + Immunotherapy + Targeted therapy
- Tislelizumab administration on days 1 and 22, and afatinib continuous administration from days 1 to 42.
- Low-dose radiotherapy, 4Gy/2f.
- Surgery.
干预措施: Tislelizumab (Drug)
Immunotherapy + Targeted therapy
- Tislelizumab administration on days 1 and 22, and afatinib continuous administration from days 1 to 42
- Surgery.
干预措施: Tislelizumab (Drug)
Immunotherapy + Targeted therapy
- Tislelizumab administration on days 1 and 22, and afatinib continuous administration from days 1 to 42
- Surgery.
干预措施: Afatinib (Drug)
Low-dose radiotherapy + Immunotherapy + Targeted therapy
- Tislelizumab administration on days 1 and 22, and afatinib continuous administration from days 1 to 42.
- Low-dose radiotherapy, 4Gy/2f.
- Surgery.
干预措施: Low dose radiotherapy (Radiation)
结局指标
主要结局
Major Pathologic Response
时间窗: Intraoperative
Major Pathologic Response (MPR) was defined as fewer than 10% viable tumor cells.
次要结局
- Pathologic Complete Response(Intraoperative)
- Objective Response Rate(From the start of neoadjuvant therapy to the end of neoadjuvant therapy, the duration is approximately 2 months.)
- Pathologic Complete Response(Intraoperative)
- Objective Response Rate(From the start of neoadjuvant therapy to the end of neoadjuvant therapy, the duration is approximately 2 months.)
研究者
Xingchen Peng
PhD, Professor
West China Hospital