A Multi-Center, Randomized Phase III Study of Neoadjuvant Anti-PD-1 Immunotherapy Plus TP Chemotherapy Versus TP Chemotherapy or Up-Front Surgery in Resectable Locally Advanced Oral Squamous Cell Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 309
- 试验地点
- 3
- 主要终点
- Event-free Survival (EFS) Rate on Each Treatment Arm.
研究概览
简要总结
The purpose of this study is to investigate the survival benefit of neoadjuvant anti-PD-1 immunotherapy plus TP chemotherapy compared with TP chemotherapy or up-front surgery in resectable locally advanced oral squamous cell carcinoma.
详细描述
On the basis of preliminary study, this study is to further verify the efficacy and safety of neoadjuvant anti-PD-1 immunotherapy plus chemotherapy. The further purpose of this study is to investigate the survival benefit of neoadjuvant anti-PD-1 immunotherapy plus TP chemotherapy compared with TP chemotherapy or up-front surgery in resectable locally advanced oral squamous cell carcinoma. And on this basis, the investigators will explore the changes of the profiles and functions of immune cells within tumors, lymph nodes and peripheral blood after the experimental interventions, as well as their correlation with the patients' response and prognosis.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically documented oral squamous cell carcinoma (biopsy required).
- •Local advanced oral squamous cell carcinoma (clinical stage T1-2N1-2M0, T3-4aN0-2M0) with resection option for potential cure, as assessed by a faculty surgeon at Hospital of Stomatology, Wuhan University.
- •Distant metastasis is excluded by chest CT and emission computed tomograph.
- •Adequate organ function as follows: 1) Leukocyte count ≥ 2,000/mm3; 2) Absolute neutrophil count ≥ 1,000/mm3; 3) Platelet count ≥ 100,000/mm3; 4) Hemoglobin ≥ 90 g/L; 5) Serum albumin ≥30 g/L; 6) Total bilirubin ≤ 1.5 × upper limit of normal (ULN); 7) AST (SGOT) and ALT (SGPT) < 2.5 × ULN; 8) ALP ≤ 2.5 × ULN; 9) Prothrombin time-international normalized ratio ≤ 1.5; 10) Serum creatinine ≤ 1.5 × ULN; 11) INR/PT≤ 1.5; 12) TSH ≤ ULN.
- •ECOG performance status 0-
- •Female patient tested HCG negative in serum or urine within 7 days prior to the start of investigational product. Both patient and partner must agree to use contraception prior to study entry and for the duration of study participation and for up to 120 days after the last dose of PD-1 blockade.
- •Patient understands the study regimen, its requirements, risks and discomforts and is able and willing to sign the informed consent form.
排除标准
- •History of ≥ 3 grade immune related adverse events (irAEs) or have not recovered to ≤ 1 grade irAEs from previous treatment.
- •History of other treatments for cancer, including surgery, chemotherapy, radiotherapy or molecular targeted therapy within past 5 years.
- •Previous therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 or any other antibody targeting T cell co-regulatory pathways.
- •Active autoimmune disease or history of refractory autoimmune disease.
- •Active systemic infection requiring therapy.
- •Patients who are receiving psychotropic drug or alcohol/drug abuse.
- •Subjects with concurrent other active malignancies.
- •HIV or untreated active HBV or HCV infections, or vaccinated (HBV, flu, varicella, etc) within 4 weeks before recruitment.
- •Uncontrollable systemic diseases, including diabetes, hypertension, etc.
- •History of stroke or transient ischemic attack within past 6 months.
- •Distant metastases or inability to resect after physician evaluation.
- •Serious cardiovascular, respiratory, immune system critical disease or other conditions that the researchers thought might increase the subjects' risk.
研究组 & 干预措施
Neoadjuvant TP chemotherapy
The participants will receive 2 courses of TP chemotherapy. Then the participants will take a radical surgery followed by radiotherapy or chemoradiotherapy if necessary.
干预措施: TP (Drug)
Neoadjuvant anti-PD-1 immunotherapy plus TP chemotherapy
The participants will receive 3 doses of PD-1 blockade and 2 courses of TP chemotherapy. Then the participants will take a radical surgery followed by radiotherapy or chemoradiotherapy if necessary.
干预措施: Camrelizumab plus TP (Drug)
结局指标
主要结局
Event-free Survival (EFS) Rate on Each Treatment Arm.
时间窗: 24 months.
EFS is the time from the date of randomization to the date of first record of disease progression as defined by RECIST 1.1.
次要结局
- Radiographic Response.(8 weeks.)
- Overall Survival (OS) on Each Treatment Arm.(24 months.)
- Pathologic Response.(8 weeks.)
- Adverse Events (AEs).(24 months.)
研究者
Gang Chen
Chief physician, Professor
Hospital of Stomatology, Wuhan University