A Randomized Controlled Clinical Study of De-Escalation Surgery Following Immunotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 356
- 试验地点
- 1
- 主要终点
- 3-year overall survival (OS) rate
研究概览
简要总结
This is a multicenter, randomized, open-label, non-inferiority clinical trial designed to evaluate whether downgraded surgery-guided by post-immunotherapy tumor boundaries-can achieve comparable 3-year overall survival (OS) to standard surgery in patients with Stage III-IVa locally advanced head and neck squamous cell carcinoma (HNSCC) who have responded to neoadjuvant immunotherapy. A total of 356 patients will be randomized 1:1 to receive either downgraded or standard surgery, followed by risk-adapted adjuvant therapy. The primary endpoint is 3-year OS, with secondary endpoints including disease-free survival, quality of life, complication rates, and cost-effectiveness. The study hypothesizes that downgraded surgery will preserve organ function and quality of life without compromising survival outcomes.
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
盲法说明
Open-label study; no parties are masked.
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 between 18 and 75 years inclusive, with no restriction on gender.
- •Histologically confirmed primary squamous cell carcinoma of the head and neck (excluding nasopharyngeal carcinoma).
- •Clinical stage III-IVa according to the AJCC 8th edition TNM staging system prior to immunotherapy; specifically, stage III-IVa for oropharyngeal squamous cell carcinoma (p16-negative) or stage III for oropharyngeal squamous cell carcinoma (p16-positive).
- •ECOG performance status of 0 or
- •Life expectancy of ≥6 months.
- •Received preoperative immune checkpoint inhibitor therapy, primarily with anti-PD-1 monoclonal antibodies or bispecific antibodies containing an anti-PD-1 arm, regardless of brand, with or without concurrent chemotherapy or targeted therapy, for no more than six cycles.
- •Achieved complete response (CR) or partial response (PR) on imaging assessment after preoperative therapy, according to RECIST 1.1 criteria.
- •Assessed as eligible for de-escalation surgery based on clinical evaluation by the surgeon. Examples include omission of surgery on the primary lesion; preservation of critical structures or functions, such as retaining the mandible initially planned for resection; avoidance of flap reconstruction; or limitation of tongue resection to less than half when hemi-glossectomy was initially indicated.
- •No prior curative surgery or radiotherapy for the current tumor.
- •Willing to undergo surgical treatment.
- •No significant contraindications to surgery.
- •Voluntary participation in the study, signed informed consent, good compliance, and willingness to cooperate with follow-up visits.
排除标准
- •Severe underlying diseases making the patient unable to tolerate surgery.
- •Current tumor is recurrent.
- •Myocardial infarction, severe/unstable angina, NYHA class II or higher heart failure, or symptomatic congestive heart failure within 6 months before randomization.
- •History of psychiatric drug abuse or drug addiction.
- •Pregnant or breastfeeding women.
- •Diagnosis of other malignancies within 5 years prior to study entry, except for locally treated and cured basal cell carcinoma or squamous cell carcinoma of the skin, superficial bladder carcinoma, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, and papillary thyroid carcinoma.
- •Any other severe physical or mental illness, or laboratory abnormalities that might increase the risk associated with participation or interfere with the study results, or any other conditions deemed unsuitable for participation by the investigator.
研究组 & 干预措施
De-escalation surgery
The surgical procedure should be designed and performed based on the tumor boundaries following neoadjuvant therapy.
干预措施: De-escalation surgery (Procedure)
De-escalation surgery
The surgical procedure should be designed and performed based on the tumor boundaries following neoadjuvant therapy.
干预措施: radiotherapy (Radiation)
De-escalation surgery
The surgical procedure should be designed and performed based on the tumor boundaries following neoadjuvant therapy.
干预措施: adjuvant immunotherapy (Drug)
Standard Surgery
The surgical procedure should be designed and performed based on the tumor boundaries prior to neoadjuvant therapy.
干预措施: Standard Surgery (Procedure)
Standard Surgery
The surgical procedure should be designed and performed based on the tumor boundaries prior to neoadjuvant therapy.
干预措施: radiotherapy (Radiation)
Standard Surgery
The surgical procedure should be designed and performed based on the tumor boundaries prior to neoadjuvant therapy.
干预措施: adjuvant immunotherapy (Drug)
结局指标
主要结局
3-year overall survival (OS) rate
时间窗: 3 years
The proportion of subjects in the intention-to-treat population who are alive at 3 years after randomization.
次要结局
- 5-year overall survival (OS) rate(5 years)
- Quality of life for HNSCC patients(Baseline, 1 months (±7d) after surgery and prior to radiotherapy, 2 months after radiotherapy, and 6 months (±14d) after randomization, 1year (±14d) after randomization)
- 3-year and 5-year Event-free survival (EFS) rates(5 years)
- incidence of adverse events(Through study completion, an average of 5 years)
- Surgical complications(Perioperative)
- Totally quality of life, QoL(Baseline, 1 months (±7d) after surgery and prior to radiotherapy, 2 months after radiotherapy, and 6 months (±14d) after randomization, 1year (±14d) after randomization)
研究者
Yue He, MD
Director of Oral and Maxillofacial & Head and Neck Oncology Department , Principal Investigator, Clinical Professor
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University