A Randomized Phase II Study of Neoadjuvant PD-1 Blockade Alone or Plus TPF Induction Chemotherapy for Resectable Local Advanced Oral Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 68
- 试验地点
- 1
- 主要终点
- Pathologic Response.
研究概览
简要总结
The purpose of this study is to investigate the safety and feasibility of neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy in subjects with resectable local advanced oral squamous cell carcinoma.
详细描述
The purpose of this study is to investigate the safety and feasibility of neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy in subjects with resectable local advanced OSCC. And on this basis, we 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 T1-2N1-3M0, T3-4aN0-3M0) 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.
研究组 & 干预措施
Neoadjuvant PD-1 blockade alone
The participants will receive 3 doses of neoadjuvant PD-1 blockade. Then the participants will take a radical surgery followed by radiotherapy or chemoradiotherapy if necessary.
干预措施: Camrelizumab (Drug)
Neoadjuvant PD-1 blockade plus TPF induction chemotherapy
The participants will receive 3 doses of PD-1 blockade and 2 courses of TPF induction chemotherapy. Then the participants will take a radical surgery followed by radiotherapy or chemoradiotherapy if necessary.
干预措施: Camrelizumanb plus TPF (Drug)
结局指标
主要结局
Pathologic Response.
时间窗: 8 weeks.
Pathologic response of resected tumors and lymph nodes to neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy. Hematoxylin and eosin (H\&E)-stained slides of entire tumor and all sampled lymph nodes were scanned and assessed by two independent pathologists. The entire tumor bed and all sampled lymph nodes were examined histologically in patients who had pathological complete response (pCR), which was defined as the absence of viable tumor in all slides. MPR was defined as the presence of 10% or less viable residual tumor in the resected tumor specimens. Pathological partial response (pPR) was defined as presence of more than 10% and less than 50% viable residual tumor and pathological non-response (pNR) was defined as presence of more than 50% viable residual tumor in the resected tumor specimens. Pathologic response was defined as sum of pCR and MPR.
次要结局
- Radiographic Response.(8 weeks.)
- Event-free Survival (EFS) Rate on Each Treatment Arm.(24 months.)
- Overall Survival (OS) on Each Treatment Arm.(24 months.)
- Adverse Events (AEs).(24 months.)
研究者
Gang Chen
Chief physician, Professor
Hospital of Stomatology, Wuhan University