A Randomized, Controlled, Phase II Clinical Study of Neoadjuvant Radio-immunotherapy Versus Immunotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Major Pathological Response (MPR) Rate
研究概览
简要总结
The purpose of this randomized Phase II study is to evaluate and compare the efficacy and safety of neoadjuvant radio-immunotherapy versus immunotherapy alone for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Participants will be randomly assigned to one of two groups. The experimental group will receive a combination of radiotherapy and Adebrelimab as neoadjuvant treatment, while the control group will receive Adebrelimab monotherapy. Following the neoadjuvant phase, all eligible patients will undergo surgical resection. The primary objective is to determine if the addition of radiotherapy improves the major pathological response (MPR) rate. Secondary objectives include pathological complete response (pCR) rate, objective response rate (ORR), and event-free survival (EFS).
详细描述
This is a randomized, controlled, open-label, Phase II clinical trial designed to compare the efficacy and safety of neoadjuvant radiotherapy combined with Adebrelimab versus Adebrelimab monotherapy in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).
Experimental Arm (Radio-immunotherapy): Patients will receive neoadjuvant radiotherapy (SBRT 24 Gy in 3 fractions) followed by or concurrent with 2 cycles of Adebrelimab (1200mg, Q3W).
Control Arm (Immunotherapy alone): Patients will receive 2 cycles of Adebrelimab (1200mg, Q3W) as monotherapy.
Following the completion of neoadjuvant therapy, a multidisciplinary team (MDT) will evaluate the patients' response. Eligible patients will then undergo standard surgical resection of the primary tumor and neck dissection within 3 to 4 weeks after the last dose of immunotherapy.
The primary endpoint is the Major Pathological Response (MPR) rate, defined as less than or equal to 10% residual viable tumor in the resected specimen. Secondary endpoints include Pathological Complete Response (pCR) rate, Objective Response Rate (ORR) according to RECIST 1.1, Event-Free Survival (EFS), and the incidence of treatment-emergent adverse events (TEAEs) graded by CTCAE 5.0.
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
Although the study is open-label due to the nature of radiotherapy intervention, the pathological assessment of the primary endpoint (Major Pathological Response, MPR) will be performed by independent pathologists who are masked to the treatment assignment to minimize bias.
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 confirmed, treatment-naive, resectable head and neck squamous cell carcinoma (HNSCC).
- •Clinical stage III to IVB (according to AJCC 8th edition), excluding HPV-positive oropharyngeal cancer.
- •PD-L1 expression with a Combined Positive Score (CPS) ≥
- •Karnofsky Performance Status (KPS) score ≥
- •Age between 18 and 70 years (inclusive).
- •Evaluated by a multidisciplinary team (MDT) as resectable or borderline resectable, and suitable for preoperative Stereotactic Body Radiotherapy (SBRT).
- •Adequate organ function within 7 days prior to enrollment, meeting laboratory criteria for hematology, liver, and renal function.
- •Anatomical requirements for SBRT: Lesions must be localized with adequate anatomical space for high-precision radiotherapy without exceeding safety limits for Organs at Risk (OARs).
- •Voluntary participation with a signed Informed Consent Form (ICF).
排除标准
- •Prior radical surgery, radiotherapy, or immunotherapy for head and neck malignancies.
- •Severe comorbidities that may interfere with study participation, such as uncontrolled cardiovascular disease or active infections.
- •Active Hepatitis B virus (HBV) infection (HBsAg positive and HBV DNA ≥ 500 IU/mL).
- •Pregnant or breastfeeding women.
- •Any other condition that, in the opinion of the investigator, makes the patient unsuitable for enrollment.
研究组 & 干预措施
Neoadjuvant Radio-immunotherapy (Adebrelimab + RT)
Patients will receive 2 cycles of neoadjuvant Adebrelimab (1200 mg, IV, Q3W) combined with radiotherapy (SBRT), followed by surgical resection.
干预措施: Adebrelimab (Drug)
Neoadjuvant Radio-immunotherapy (Adebrelimab + RT)
Patients will receive 2 cycles of neoadjuvant Adebrelimab (1200 mg, IV, Q3W) combined with radiotherapy (SBRT), followed by surgical resection.
干预措施: radiotherapy (Radiation)
Neoadjuvant Immunotherapy Monotherapy (Adebrelimab)
Patients will receive 2 cycles of neoadjuvant Adebrelimab (1200 mg, IV, Q3W) monotherapy, followed by surgical resection.
干预措施: Adebrelimab (Drug)
结局指标
主要结局
Major Pathological Response (MPR) Rate
时间窗: At the time of surgery (approximately 6-8 weeks after the first dose of neoadjuvant therapy).
The percentage of participants with 10% or less residual viable tumor cells in the resected primary tumor and lymph nodes following neoadjuvant therapy. Assessment will be performed by independent pathologists.
次要结局
- Pathological Complete Response (pCR) Rate(At the time of surgery.)
- Objective Response Rate (ORR)(From the first dose of neoadjuvant therapy until pre-operative clinical evaluation (approximately 6 weeks).)
- Incidence of Treatment-Emergent Adverse Events (TEAEs)(From the start of treatment up to 30 days after surgery.)
研究者
Chen Chunyan
Professor
Sun Yat-sen University