A Prospective, Single-Arm Clinical Trial of Iparomlimab and Tuvonralimab Combined With Spatially Fractionated Radiotherapy and Definitive Chemoradiotherapy in Locoregionally Advanced Bulky 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
- 25
- 试验地点
- 1
- 主要终点
- 2-year EFS (Event - Free Survival)
研究概览
简要总结
Study Objectives
- Primary Objective:
The core aim of this study is to investigate whether the sequential approach of Spatially Fractionated Radiotherapy followed by 3 cycles of induction chemotherapy combined with Iparomlimab and Tuvonralimab, definitive chemoradiotherapy, and maintenance therapy with the Iparomlimab and Tuvonralimab can improve the 2-year event-free survival (EFS) rate in patients with locoregionally advanced bulky head and neck squamous cell carcinoma (HNSCC). 2. Secondary Objectives:s
To analyze the impact of this integrated treatment regimen on key efficacy endpoints, including:
Objective response rate (ORR), Duration of response (DoR), Distant metastasis-free survival (DMFS), Local region recurrence-free survival (LRRFS), Overall survival (OS)。 2. Study Endpoints
(1) Primary Endpoint and Definition: 2-Year Event-Free Survival (EFS) Rate (2) Secondary Endpoints and Definitions:
- 2-Year Overall Survival (OS) Rate
- 2-Year Distant Metastasis-Free Survival (DMFS) Rate.
- 2-Year Local Region Recurrence-Free Survival (LRRFS) Rate.
- Objective Response Rate (ORR).
- Duration of Response (DoR).
- Quality of Life (QoL):
Assessed across multiple domains:
Physical Function: Measured via tools like the 6-minute walk test or ADL (Activities of Daily Living) scale.
Psychological Status: Evaluated using instruments such as HAMD (Hamilton Anxiety and Depression Scale) or MMSE (Mini-Mental State Examination).
Social Function: Assessed via social engagement questionnaires (e.g., HAQ-DI [Health Assessment Questionnaire-Disability Index]).
Spiritual Well-being: Evaluated using tools like PIL (Purpose in Life test). Clinically meaningful improvements in these domains before and after treatment define successful QoL endpoints (e.g., positive changes in physical, psychological, social, and spiritual health in cardiac patients). 7. Safety:
The nature and severity of adverse reactions associated with the treatment. 8. Tolerability:
The degree to which patients can endure treatment-related side effects.
详细描述
I. Study Design and Technical Route Details 1. Stratified Implementation of Treatment Protocols
- Spatially Fractionated Radiotherapy (SFRT) Phase Technical Parameters: Three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) is used to deliver a single high-dose fraction to the primary tumor and bulky metastatic lymph nodes (≥5 cm), with a prescribed dose of 10-20Gy/1 fraction. Dose-volume histogram (DVH) optimization ensures target coverage while limiting doses to organs at risk (e.g., spinal cord ≤45Gy, parotid gland mean dose ≤26Gy).
Timing: A positioning CT scan (slice thickness ≤3 mm) is completed within 7 days of enrollment. The radiation oncologist contours the target volumes, and the physicist designs the treatment plan, which is reviewed by a multidisciplinary team (MDT) before implementation. 2. Induction Chemotherapy Combined with Immunotherapy Phase
Drug Regimen:
Docetaxel: 75mg/m², intravenous drip, d1, Q3W for 3 cycles (body surface area calculated using measured height and weight, precise to 0.01m²).
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 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, both sexes eligible;
- •Histologically confirmed head and neck squamous cell carcinoma (HNSCC), diagnosed as locoregionally advanced disease with measurable primary tumor and/or cervical metastatic lymph nodes >5 cm in maximum diameter, and deemed unresectable by surgical evaluation;
- •Treatment-naive (no prior anti-tumor therapy);
- •At least one measurable lesion (excluding brain metastases) per RECIST 1.1 criteria;
- •ECOG performance status 0-1;
- •Life expectancy ≥12 weeks;
- •Organ function meeting the following criteria (no blood products, colony-stimulating factors, leukocyte/ thrombocyte/ erythrocyte-stimulating agents within 14 days prior to first study drug administration):
- •Absolute neutrophil count (ANC) ≥1.5×10^9/L;
- •Platelets ≥90×10^9/L;
- •Hemoglobin ≥8 g/dL;
- •Serum albumin ≥2.8 g/dL;
- •Total bilirubin ≤1.5×ULN, ALT/AST/ALP ≤2.5×ULN; if liver metastases present, ALT/AST ≤5×ULN; if liver/bone metastases present, ALP ≤5×ULN;
- •Serum creatinine ≤1.5×ULN or creatinine clearance >60 mL/min;
- •APTT and INR ≤1.5×ULN (patients on stable anticoagulation [e.g., LMWH, warfarin] with therapeutic INR acceptable for screening).
- •Voluntary informed consent, good compliance, and willingness to cooperate with follow-up;
- •Investigator determination of potential benefit.
排除标准
- •Those with a history of severe immediate - type allergic reactions to any of the drugs used in this study；
- •Within six months before screening, having any of the following conditions: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass grafting, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism. Patients known to have coronary artery disease, congestive heart failure that doesn't meet the above criteria, or a left ventricular ejection fraction of less than 50% must have an optimally stable medical regimen as determined by the treating physician. If appropriate, a cardiologist can be consulted；
- •Individuals who have received anti - tumor vaccines or live vaccines within four weeks before the first administration of the study drug；
- •Patients with active autoimmune diseases or a history of autoimmune diseases that are likely to relapse. The following patients are not excluded and can proceed to further screening:
- •Those with well - controlled type 1 diabetes.
- •Patients with hypothyroidism that can be controlled with hormone replacement therapy alone.
- •People with skin diseases that do not require systemic treatment, such as vitiligo, psoriasis, and alopecia.
- •Any other diseases that are not expected to relapse without external triggers；
- •Those lacking full or restricted civil capacity；
- •Patients with physical or mental disorders who, in the investigator's opinion, are unable to fully or adequately understand the potential complications of this study；
- •Patients with an expected survival time of less than three months；
- •Patients with significantly reduced functions of the heart, liver, lungs, kidneys, and bone marrow；
- •Those with a history of substance abuse or alcohol addiction；
- •Patients whose tumor lesions invade large blood vessels, such as the internal carotid artery and jugular vein and their main branches, with a high risk of bleeding；
- •Subjects who need systemic treatment with corticosteroids (more than 10 mg/day prednisone equivalent) or other immunosuppressants within two weeks before the first use of the study drug, except for the use of corticosteroids for local esophageal inflammation and the prevention of allergies, nausea, and vomiting. In other special cases, communication with the sponsor is required. In the absence of active autoimmune diseases, the inhalation or local use of steroids and adrenal cortical hormone replacement at a dose higher than 10 mg/day prednisone equivalent is allowed；
- •Those with a history of immunodeficiency, including HIV - positive results, other acquired or congenital immunodeficiency diseases, or a history of organ transplantation and allogeneic bone marrow transplantation；
- •Pregnant or lactating female patients, as well as male or female patients who are fertile but unwilling or unable to use contraception throughout the study and for at least one year after the end of the treatment plan；
- •Patients who, in the investigator's opinion, are not suitable for inclusion.
研究组 & 干预措施
Study of Iparomlimab and Tuvonralimab Combined With SFRT and Definitive Chemoradiotherapy in HNSCC
This is a single-arm study.(1) Induction therapy: Administer Spatially Fractionated Radiotherapy to the tumor at a dose of 10 - 20 Gy in 1 fraction. Subsequently, conduct 3 cycles of induction chemotherapy (docetaxel 75 mg/m² on day 1, cisplatin 25 mg/m² from day 1 to day 3, every 3 weeks for 3 cycles) combined with immunotherapy using Iparomlimab and Tuvonralimab (5 mg/kg on day 1, every 3 weeks for 3 cycles).
(2) Concurrent chemoradiotherapy: Initiate radical concurrent chemoradiotherapy within 2 - 4 weeks after the completion of induction therapy. The prescribed dose of radical radiotherapy is 70 Gy for the primary tumor and 66 - 70 Gy for the positive cervical lymph nodes, to be delivered in 30 - 33 fractions. Concurrent chemotherapy involves intravenous.
(3) Maintenance therapy: Start maintenance immunotherapy with Iparomlimab and Tuvonralimab 4 - 6 weeks after the completion of concurrent chemoradiotherapy. Administer it at a dose of 5 mg/kg per administration.
干预措施: Iparomlimab and Tuvonralimab Injection (Drug)
结局指标
主要结局
2-year EFS (Event - Free Survival)
时间窗: 2 years
Event-Free Survival (EFS) rate: Defined as the time from enrollment to the occurrence of the first event among any of the following: disease progression (including local progression and distant metastasis), recurrence (i.e., reappearance of the tumor after treatment in cancer patients), death from any cause, etc. In other words, it represents the survival duration during the observation period when patients do not experience these predefined "events".
次要结局
- 2 - year Overall Survival (OS) rate(2 years)
- 2 - year Distant Metastasis - Free Survival (DMFS) rate(2 years)
- 2 - year Local Region Recurrence - Free Survival (LRRFS) rate(2 years)
- Overall Response Rate (ORR)(2 years)
- Duration of Response (DoR)(2 years)
- Safety(treatment-related toxicity and adverse reactions)(2 years)
- Patients' Quality of Life(2 years)