Anti-PD-1 Therapy in Locoregionally Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma: A Multicenter, Randomized Controlled Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 217
- 主要终点
- Event-Free Survival (EFS)
研究概览
简要总结
The goal of this clinical trial is to determine whether a perioperative PD-1 antibody-based treatment strategy, consisting of neoadjuvant PD-1 antibody plus chemotherapy followed by adjuvant PD-1 antibody after surgery, improves outcomes compared with the current standard treatment in patients with resectable locally recurrent head and neck squamous cell carcinoma (HNSCC). The study will also evaluate the safety of this perioperative treatment approach.
The main questions it aims to answer are:
Does perioperative PD-1 antibody-based therapy improve event-free survival compared with the current standard treatment? What adverse events occur during treatment with neoadjuvant PD-1 antibody plus chemotherapy and adjuvant PD-1 antibody?
Researchers will compare a perioperative PD-1 antibody-based treatment strategy with the current standard treatment to determine which approach provides better clinical outcomes.
Participants will:
Be randomly assigned to one of two study groups. Receive either neoadjuvant PD-1 antibody plus chemotherapy followed by surgery and adjuvant PD-1 antibody, or undergo upfront surgery followed by standard postoperative treatment as indicated.
Visit the clinic regularly for physical examinations, blood tests, imaging assessments, and other study procedures.
Be followed after treatment to monitor disease status, treatment response, survival outcomes, and adverse events.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: 18 to 80 years old (inclusive).
- •Primary Tumor: Histologically or cytologically confirmed head and neck squamous cell carcinoma (excluding nasopharyngeal carcinoma). Patients must have previously received surgery and/or radiotherapy.
- •Diagnosis: Locally recurrent or metastatic disease confirmed by pathology and/or imaging.
- •Clinical Stage: T1-4a, N0-2, M0 (AJCC TNM Staging System, 8th Edition), with no evidence of distant metastasis, and the recurrent lesion is assessed as surgically resectable.
- •Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life Expectancy: Expected survival ≥ 6 months.
- •Immunotherapy: No significant contraindications to immunotherapy.
- •Consent to Surgery: Willing to undergo surgical treatment.
- •Adequate Organ Function:
- •Hematology (without transfusion or hematopoietic growth factor support within 14 days): WBC ≥ 4.0 × 10⁹/L, ANC ≥ 1.5 × 10⁹/L, Platelets ≥ 100 × 10⁹/L, Hemoglobin ≥ 90 g/L.
- •Biochemistry: Serum albumin ≥ 3.0 g/dL (30 g/L), Total bilirubin (TBIL) ≤ 1.5 × ULN, ALT and AST ≤ 2.5 × ULN, BUN and Creatinine ≤ 1.5 × ULN, or calculated creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula).
- •Coagulation: Adequate coagulation function defined as International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 × ULN. For participants receiving anticoagulant therapy, PT must be within the intended therapeutic range of the anticoagulant.
- •Contraception: Female participants of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment and must agree to use effective contraception during the study and for 6 months after the last dose of the anti-PD-1 antibody. Male participants with female partners of childbearing potential must agree to use effective contraception during the study and for 6 months after the last dose of the anti-PD-1 antibody.
- •Informed Consent: The participant must voluntarily join the study, sign the informed consent form, be compliant, and be willing to cooperate with follow-up.
排除标准
- •Prior treatment with anti-PD-1/PD-L1 antibodies, anti-PD-L2 antibodies, anti-CD137 antibodies, CTLA-4 antibodies, or other drugs/antibodies targeting T-cell co-stimulation or checkpoint pathways.
- •Presence of active severe autoimmune disease. Participants with conditions that are stable and do not require systemic immunosuppressive therapy are eligible, such as: Type I diabetes mellitus, hypothyroidism requiring only hormone replacement therapy, and skin conditions not requiring systemic treatment (e.g., vitiligo, psoriasis, and alopecia).
- •Has a congenital or acquired immunodeficiency (e.g., HIV infection), active hepatitis B (HBV-DNA ≥ 10⁴ copies/mL), or active hepatitis C (positive hepatitis C antibody and HCV-RNA above the lower limit of detection of the assay).
- •Known allergy to the study drug or any of its excipients; or a history of severe allergic reactions to other monoclonal antibodies.
- •Occurrence of any of the following within 6 months prior to randomization: myocardial infarction, severe/unstable angina pectoris, cardiac insufficiency of NYHA Class 2 or higher, clinically significant supraventricular or ventricular arrhythmias, or symptomatic congestive heart failure.
- •Vaccination with a live vaccine within 4 weeks prior to the first dose of the study drug. Inactivated virus vaccines for seasonal influenza administered via injection are permitted; however, intranasal live attenuated influenza vaccines are not permitted.
- •Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
- •Known history of psychoactive substance abuse or drug addiction.
- •Pregnant or breastfeeding women.
- •Diagnosis of any other malignancy within 5 years prior to study entry, with the exception of locally treated and cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, cervical carcinoma in situ, ductal carcinoma in situ of the breast, and papillary thyroid cancer.
- •Presence of any other severe physical or mental illness or laboratory abnormality that may increase the risk of participating in the study, interfere with the study results, or render the participant unsuitable for participation in the study, as judged by the investigator.
研究组 & 干预措施
Neoadjuvant Chemoimmunotherapy
Participants will receive 2-4 cycles of neoadjuvant PD-1 antibody plus chemotherapy every 3 weeks, followed by surgery and postoperative radiotherapy or chemoradiotherapy as clinically indicated. PD-1 antibody will be continued as adjuvant therapy for up to 15 cycles.
干预措施: Neoadjuvant PD-1 antibody plus chemotherapy (Drug)
Neoadjuvant Chemoimmunotherapy
Participants will receive 2-4 cycles of neoadjuvant PD-1 antibody plus chemotherapy every 3 weeks, followed by surgery and postoperative radiotherapy or chemoradiotherapy as clinically indicated. PD-1 antibody will be continued as adjuvant therapy for up to 15 cycles.
干预措施: surgery (Procedure)
Neoadjuvant Chemoimmunotherapy
Participants will receive 2-4 cycles of neoadjuvant PD-1 antibody plus chemotherapy every 3 weeks, followed by surgery and postoperative radiotherapy or chemoradiotherapy as clinically indicated. PD-1 antibody will be continued as adjuvant therapy for up to 15 cycles.
干预措施: Adjuvant PD-1 antibody (Drug)
Upfront Surgery
Participants will undergo upfront surgery with or without postoperative radiotherapy or chemoradiotherapy.
干预措施: surgery (Procedure)
结局指标
主要结局
Event-Free Survival (EFS)
时间窗: 2 years after randomization
Event-free survival (EFS) is defined as the time from randomization to the first occurrence of disease recurrence or metastasis after surgery; disease progression according to RECIST version 1.1 that prevents definitive surgery during preoperative treatment or occurs in participants who do not undergo definitive surgery; a second primary malignancy; or death from any cause. Disease progression during preoperative treatment that does not prevent definitive surgery is not considered an EFS event. Failure to undergo definitive surgery for reasons other than disease progression is not itself considered an EFS event. Participants without an EFS event will be censored at the date of the last adequate disease assessment. EFS will be estimated using the Kaplan-Meier method. The planned primary EFS analysis will be performed after all participants have had the opportunity for at least 24 months of follow-up after randomization.
次要结局
- Overall Survival (OS)(2 years after randomization)
- 5-Year Event-Free Survival (EFS)(5 years after randomization)
- 5-Year Overall Survival (OS)(5 years after randomization)
- Adverse Events and Serious Adverse Events(From initiation of assigned treatment through 30 days after treatment completion or discontinuation; serious adverse events and adverse events of special interest through 90 days after treatment completion or discontinuation.)
- Pathologic Complete Response (pCR) Rate(Within 2 weeks after surgery)
- Major Pathologic Response (MPR) Rate(Within 2 weeks after surgery)
- Objective Response Rate (ORR)(At the preoperative tumor assessment after completion of 2 to 4 cycles of neoadjuvant treatment (each cycle is 21 days; approximately 6 to 12 weeks after initiation of neoadjuvant treatment).)
研究者
Yanjie Zhang, MD
Chief physician and professor
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University