NCT07776340尚未招募2 期
Induction Chemoimmunotherapy Followed by Concurrent Chemoradiotherapy and Adjuvant Immunotherapy Versus Concurrent Chemoradiotherapy Alone in Unresectable or Inoperable Locoregionally Advanced HPV-Negative Head and Neck Squamous Cell Carcinoma: A Randomized, Controlled, Phase 2 Study
适应症
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 104
- 试验地点
- 1
- 主要终点
- Event-free Survival (EFS)
研究概览
简要总结
The goal of this clinical trial is to evaluate if adding chemotherapy and immunotherapy as induction treatment prior to definitive chemoradiotherapy could improve the outcomes of locally advanced HPV-negative head and neck squamous cell that are not amenable to surgery. The study aims to answer:
- Does this treatment improve the survival outcomes of participants?
- How do the tumors of participants response to the treatment?
- How is the safety of this treatment? Researchers will compare this treatment (induction chemoimmunotherapy, followed by concurrent chemoradiotherapy, and then immunotherapy as maintenance therapy) to concurrent chemoradiotherapy to see whether it provides additional clinical benefits.
详细描述
This multicenter, prospective, open-label, phase II randomized controlled clinical trial plans to enroll 104 treatment naïve participants with locally advanced (III-IVB by UICC/AJCC 8th), unresectable or inoperable HPV-negative head and neck squamous cell carcinoma (HNSCC). Patients will be stratified by primary tumor site (oropharynx vs. non-oropharynx) and randomly assigned (1:1) to one of two treatment arms: (1) Arm A (Experimental): Induction phase, three cycles of tislelizumab plus paclitaxel and cisplatin; Concurrent chemoradiotherapy (CCRT) phase, definitive radiotherapy concurrent with two cycles of cisplatin; Adjuvant phase, 13 cycles of tislelizumab. (2) Arm B (Comparator): CCRT, definitive radiotherapy concurrent with two cycles of cisplatin. The primary hypothesis is that the addition of induction chemoimmunotherapy and adjuvant immunotherapy improves event-free survival compared to chemoradiotherapy alone.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pathologically confirmed HPV-negative head and neck squamous cell carcinoma (including laryngeal, hypopharyngeal, or oropharyngeal cancer).
- •Loco-regionally advanced (Stage III-IVB) disease according to the 8th edition clinical staging system of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC).
- •Confirmed by a multidisciplinary team (MDT) as not amenable to curative surgery and deemed suitable for definitive concurrent chemoradiotherapy.
- •"Not amenable to curative surgery" includes unresectable disease (anatomic impossibility of resection) or inoperable disease (patient medically unable to tolerate or declining surgical resection).
- •ECOG performance status of 0-
- •Pre-treatment neutrophils ≥ 1.5 × 10⁹/L, hemoglobin ≥ 90 g/L, platelets ≥ 100 × 10⁹/L; total bilirubin ≤ 1.5 × upper limit of normal (ULN), ALT ≤ 1.5 × ULN, AST ≤ 1.5 × ULN, ALP ≤ 2.5 × ULN; creatinine ≤ 1.5 × ULN.
- •Activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤ 1.5 × ULN (patients on a stable dose of anticoagulant therapy, such as low molecular weight heparin or warfarin, with an INR within the therapeutic range for the anticoagulant, are eligible for screening).
- •Normal pulmonary and cardiac function.
- •Normal myocardial enzyme profile.
- •No prior radiotherapy, chemotherapy, immunotherapy, or biological targeted therapy, or any other antitumor treatment for the current tumor lesion(s).
- •Women of childbearing potential must have a negative pregnancy test (serum) within 7 days before enrollment and must voluntarily use appropriate contraception during the observation period and for 8 weeks after the last treatment; for men, they must be surgically sterile or agree to use appropriate contraception during the observation period and for 8 weeks after the last treatment.
- •Participants must sign informed consent and be willing and able to comply with the requirements of visits, treatment, laboratory tests and other research requirements stipulated in the research schedule.
排除标准
- •Has a history or presence of other malignancies, except for those that have been cured and with no evidence of disease for over 5 years (such as basal cell carcinoma of the skin, carcinoma in situ of the cervix, and papillary thyroid carcinoma, etc.).
- •Has active autoimmune diseases or a history of autoimmune diseases (e.g., interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); excluding autoimmune-mediated hypothyroidism stabilized with thyroid hormone replacement therapy; type I diabetes mellitus stabilized on insulin regimen; vitiligo or childhood asthma/allergies that have resolved and require no intervention in adulthood.
- •Has uncontrolled cardiac clinical symptoms or diseases, such as: (a) NYHA Class II or above heart failure; (b) unstable angina; (c) myocardial infarction within the past year; (d) clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention.
- •Has severe infection (CTCAE > Grade 2) within 4 weeks prior to the first dose of the study drug, active infection during screening, or unexplained fever > 38.5°C before administration (tumor-related fever may be considered for inclusion).
- •Has a history of allergy to any component of anti-PD-1 antibodies, paclitaxel-based drugs, or cisplatin.
- •Prior radiotherapy, chemotherapy, immunotherapy (including PD-1, anti-PD-L1 antibodies, anti-CTLA-4 antibodies, cancer vaccines, etc.), or biological targeted therapy for the current hypopharyngeal/laryngeal/oropharyngeal cancer.
- •Concurrent participation in another clinical study, unless it is an observational (non-interventional) study or the follow-up phase of an interventional study.
- •Requirement for systemic treatment with corticosteroids (prednisone equivalent dose > 10 mg/day) or other immunosuppressive agents within 2 weeks prior to the first dose of the study drug, except for topical use to manage local inflammation, prevent allergies, or manage nausea and vomiting. Other special cases should be discussed with the investigator. Inhaled or topical steroids and physiological doses of corticosteroid replacement for adrenal insufficiency (≤ 10 mg/day prednisone equivalent) are permitted in the absence of active autoimmune disease.
- •Major surgery or severe trauma within 4 weeks prior to the first dose of the study drug.
- •Has a history of immunodeficiency, including positive HIV test, other acquired or congenital immunodeficiency diseases, or history of organ transplantation or allogeneic bone marrow transplantation.
- •Has a history of interstitial lung disease (excluding radiation pneumonitis not treated with steroids) or non-infectious pneumonitis.
- •Has a history or CT evidence of active tuberculosis infection, or history of active tuberculosis infection within 1 year prior to enrollment, or history of active tuberculosis infection more than 1 year ago without formal treatment.
- •Active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10⁴ copies/mL) or hepatitis C (positive HCV antibody with HCV-RNA above the lower limit of detection of the assay).
- •Known history of drug abuse, alcohol abuse, or substance addiction
- •Pregnant or lactating women.
- •Other factors considered by the investigator that may lead to premature termination of the study, such as other severe diseases (including psychiatric disorders) requiring combined treatment, severely abnormal laboratory test values, family or social factors, or any other circumstances that may compromise subject safety or integrity of the study data.
结局指标
主要结局
Event-free Survival (EFS)
时间窗: 2 year
Defined as the time to the earliest occurrence of progressive disease that precluded chemoradiotherapy or prevented completion of chemoradiotherapy, disease recurrence, or death from any cause.
次要结局
- Overall Survival (OS)(2 year)
- Locoregional Recurrence-Free Survival (LRFS)(2 year)
- Distant Metastasis-free survival (DMFS)(2 year)
- Objective Response Rate (ORR)(Through study completion, an average of 1 year)
- Incidence of Adverse Events(2 year)
- Quality of Life (QoL) (EORTC QLQ-H&N35)(Baseline and up to 6 months)
- Quality of life (Qol) (FACT-HN)(Baseline and up to 6 months)
研究者
Chaosu Hu
Clinical Professor
Fudan University
研究点 (1)
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