SBRT Followed by Neoadjuvant Chemoimmunotherapy Before Surgery in Resectable Locally Advanced Oral and HPV-unrelated Oropharyngeal Squamous Cell Carcinoma: a Randomized Controlled Phase III Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 184
- 试验地点
- 1
- 主要终点
- 2-year event-free survival
研究概览
简要总结
The objective of this study is to evaluate the efficacy of neoadjuvant stereotactic body radiation therapy (SBRT) in combination with chemotherapy and immunotherapy, prior to radical surgery, in enhancing the 2-year event-free survival rate and overall survival rate in patients diagnosed with locally advanced oral or HPV-unrelated oropharyngeal cancer.
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
- •The inclusion criteria for this study are as follows:
- •Histologically and/or cytologically confirmed treatment-naïve oral squamous cell carcinoma or HPV-negative oropharyngeal squamous cell carcinoma.
- •Clinical stage III -Ⅳa (8th edition of AJCC).
- •Age: 18 to 75 years old.
- •According to the Eastern Cooperative Oncology Group (ECOG) criteria (with a performance status score of 0 or 1).
- •Good organ function.
- •Expected survival time: ≥ 3 months.
- •The patient has signed the informed consent form and is willing and able to comply with the study's scheduled visits, treatment plans, laboratory tests, and other research procedures.
- •Females of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to enrolment and must agree to use highly effective contraceptive measures during the study period and for at least 60 days after the last dose (including chemotherapeutic drugs and Tislelizumab).
- •If the female partner of a male subject is still of childbearing potential, the male subject must agree to use highly effective contraceptive measures during the study period and for at least 60 days after the last dose.
排除标准
- •Patients with concurrent other malignant tumors
- •Patients with known or suspected autoimmune diseases, including dementia and epilepsy.
- •Patients with severe mental disorders at the same time
- •Patients with necrotic lesions who are assessed by the investigator as having a risk of massive hemorrhage
- •Patients with severe heart disease or pulmonary dysfunction, and those with cardiac or pulmonary function grade ≤ 3 (grade 3 inclusive)
- •Patients with laboratory test results that do not meet the relevant criteria within 7 days prior to enrollment
- •Received systemic or local glucocorticoid therapy within 4 weeks prior to enrollment
- •Patients with comorbidities requiring long-term treatment with immunosuppressive drugs, or requiring systemic or local administration of corticosteroids at immunosuppressive doses.
- •Patients with active tuberculosis (TB), who are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year prior to screening.
- •A history of prior use of anti-Tislelizumab, anti-PD-L1 antibodies, anti-PD-L2 antibodies, or anti-CTLA-4 antibodies (or any other antibodies targeting T-cell co-stimulation or checkpoint pathways).
- •Subjects with any active autoimmune diseases or a history of autoimmune diseases (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism); subjects with vitiligo or those whose childhood asthma has been completely relieved and who do not require any intervention in adulthood are eligible for enrollment; those with asthma requiring medical intervention with bronchodilators are not eligible for enrollment.
- •HIV-positive subjects
- •Positive for HBsAg with concurrent positive HBV DNA copy number (quantitative test ≥ 1000 cps/ml); positive for chronic hepatitis C on blood screening (HCV antibody positive)
- •Received any anti-infective vaccines (such as influenza vaccine, varicella vaccine, etc.) within 4 weeks prior to enrollment
- •Pregnant women with positive pregnancy test results among females of childbearing potential and lactating women.
研究组 & 干预措施
Surgery arm
Radical surgery followed by postoperative radiotherapy or chemoradiotherapy.
干预措施: Surgery and postoperative radiotherapy or chemoradiotherapy (Combination Product)
Neoadjuvant treatment followed by surgery arm
Initially, the patient underwent neoadjuvant treatment, including stereotactic body radiotherapy (SBRT) followed by chemoimmunotherapy of Tislelizumab (200 mg), Docetaxel (75 mg/m²), and Cisplatin (75 mg/m²). A subsequent imaging re-examination is to be performed for assessment two weeks after the last chemotherapy cycle. Finally, curative surgical resection should be performed 3-4 weeks after the last chemotherapy cycle, followed by adjuvant postoperative radiotherapy or chemoradiotherapy.
干预措施: Neoadjuvant treatment of SBRT plus chemoimmunotherapy followed by surgery and postoperative radiotherapy or chemoradiotherapy (Combination Product)
结局指标
主要结局
2-year event-free survival
时间窗: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to two years.
The time interval from randomization to the occurrence of imaging tumor progression during the neoadjuvant treatment stage that makes surgery impossible, or postoperative imaging or biopsy results show local tumor recurrence, lymph node recurrence, distant metastasis, or death for any cause.
次要结局
- Incidence rates of AEs (Adverse Events) and SAEs (Serious Adverse Events)(Through study completion, an average of 3 year)
- Quality of life assessment(Postoperatively at 24 months)
- 2-year overall survival(From date of randomization until the date of death from any cause, assessed up to two years.)
- MPR(Three weeks after surgery)
- pCR(Three weeks after surgery)
- Mandibular Preservation Rate(On the day of surgery)
研究者
Fang-Yun Xie
Clinical Professor
Sun Yat-sen University