Randomized, Placebo-controlled, Double-blind Phase II Clinical Trial of Neoadjuvant and Adjuvant Anti-PD-1 Antibody Toripalimab Immunotherapy Combined With Concurrent Chemoradiotherapy for High-risk Nasopharyngeal Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Progress-free survival (PFS)
研究概览
简要总结
This is a randomized Phase II trial to study the effectiveness and toxicity of neoadjuvant and adjuvant PD-1 antibody Toripalimab combined with concurrent cisplatin chemoradiotherapy versus cisplatin concurrent chemoradiotherapy plus placebo in treating patients with high risk locoregionally advanced nasopharyngeal carcinoma.
详细描述
Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. For locoregionally advanced NPC, especially for the high risk NPC (plasma EBV DNA ≥ 1500 copies/ml), the incidence of treatment failure is still high. Although concurrent chemoradiotherapy (CCRT) can improve the treatment outcomes of these patients, approximately 25% of locoregionally advanced NPCs still develop relapse and metastasis.
Hence, there is an urgent need for novel therapies to improve survival and reduce treatment-related toxicity in NPC patients. Accumulating evidence shows that PD-1 antibody is effective for treating recurrent/metastastic NPC patients. This is a Phase II randomized trial to study the effectiveness and toxicity of neoadjuvant and adjuvant PD-1 antibody Toripalimab combined with CCRT versus CCRT plus placebo in treating patients with high risk NPC (Stage III-IVa, AJCC 8th and EBV DNA ≥ 1500 copies/ml).
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma, including WHO II or III Original clinical staged as III-IVa （according to the 8th AJCC edition）
- •No evidence of distant metastasis (M0)
- •Plasm EB Virus DNA≥1500copies/ml
- •Male and no pregnant female
- •Satisfactory performance status: ECOG (Eastern Cooperative OncologyGroup) scale 0-1
- •WBC ≥ 4×109 /L and PLT ≥4×109 /L and HGB ≥90 g/L
- •With normal liver function test (ALT、AST ≤ 2.5×ULN, TBIL≤ 2.0×ULN)
- •With normal renal function test ( creatinine clearance ≥60 ml/min)
排除标准
- •Patients have evidence of relapse or distant metastasis
- •Histologically confirmed keratinizing squamous cell carcinoma (WHO I)
- •Receiving radiotherapy or chemotherapy previously
- •The presence of uncontrolled life-threatening illness
- •Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
- •Suffered from other malignant tumors (except the cure of basal cell carcinoma or uterine cervical carcinoma in situ) previously.
- •Patients who have been treated with inhibitors of immune regulation (CTLA-4, PD-1, PD-L1, etc.).
- •Patients with immunodeficiency disease and history of organ transplantation.
- •Patients who have used large doses of glucocorticoids, anti-cancer monoclonal antibodies, and other immunosuppressive agents within 4 weeks.
- •HIV positive.
- •Patients with significantly lower heart, liver, lung, kidney and bone marrow function.
- •Severe, uncontrolled medical conditions and infections.
- •At the same time using other test drugs or in other clinical trials.
- •Refusal or inability to sign informed consent to participate in the trial.
- •Other treatment contraindications.
- •Emotional disturbance or mental illness, no civil capacity or limited capacity for civil conduct.
- •Hepatitis B surface antigen (HBsAg) positive and HBVDNA ≥1000cps/ml.
- •Patients with positive HCV antibody test results can only be included in the study when the polymerase chain reaction of HCV RNA is negative.
研究组 & 干预措施
Neoadjuvant and Adjuvant Toripalimab+CCRT
Drug: Cisplatin cisplatin 100mg/m2(every three weeks),D1,D22,D43 of intensity modulated radiotherapy Other Names: DDP Drug: Toripalimab Toripalimab 240mg every 2 weeks with a total of 2 cycles as neoadjuvant anti-PD-1 immunotherapy; Toripalimab240mg every 3 weeks with a total of 8 cycles as adjuvant anti-PD-1 immunotherapy 2 weeks after CCRT Other Names:anti-PD-1 antibody, JS001
干预措施: Cisplatin+Toripalimab (Drug)
Neoadjuvant and Adjuvant Placebo+CCRT
Drug: Cisplatin cisplatin 100mg/m2(every three weeks),D1,D22,D43 of intensity modulated radiotherapy Other Names: DDP Drug: placebo placebo 240mg every 2 weeks with a total of 2 cycles as neoadjuvant treatment; placebo 240mg every 3 weeks with a total of 8 cycles as adjuvant treatment 2 weeks after CCRT.
干预措施: Cisplatin+placebo (Drug)
结局指标
主要结局
Progress-free survival (PFS)
时间窗: 2 years
Defined from date of randomization to date of first documentation of progression or death due to any cause, whichever occurred first.
次要结局
- Distant Metastasis-Free Survival (DMFS)(2 years)
- Incidence rate of adverse events (AEs)(2 years)
- Number of subjects with major pathologic response (MPR)(21-28 days)
- Objective Response Rate （ORR）(After the completion of the neoadjuvant PD-1 antibody and chemoradiotherapy treatment)
- Correlation between the plasma EBV DNA level and PFS(2 years)
- Overall Survival (OS)(2 years)
- Locoregional Relapse-Free Survival (LRRFS)(2 years or until the date of the last follow-up visit.)
- Correlation between the percentage of tumor-infiltrating lymphocytes (TILs) and PFS(2 years)
- Correlation between pre-treatment PD-L1 expression level and PFS(2 years)
- Change of QoL (quality of life)(1 year)
研究者
Hai-Qiang Mai,MD,PhD
Deputy Director of the Department of Nasopharyngeal Carcinoma
Sun Yat-sen University