A Randomized Phase II Non-inferiority Study of Two Cycles Versus Three Cycles of Cisplatin Based Concurrent Chemoradiotherapy for Low Risk Locoregionally Advanced Nasopharyngeal Carcinoma Based on Pretreatment Plasma EBV DNA Level
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 236
- 试验地点
- 1
- 主要终点
- Progress-free survival
研究概览
简要总结
This is a Phase II trial to study the effectiveness of two cycles versus three cycles of Concurrent Chemoradiotherapy in treating patients with Low Risk Locoregionally Advanced Nasopharyngeal Carcinoma based on pretreatment plasma EBV DNA.
详细描述
Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. Several prospective randomized trials have demonstrated that concurrent chemoradiotherapy was superior to radiotherapy alone in the treatment of locoregionally advanced NPC. Concurrently, although cisplatin-based concurrent chemoradiotherapy was considered as the standard regimen for locoregionally advanced nasopharyngeal carcinoma, several prospective randomized trials have demonstrated that only 52-63% patients can finished three cycles cisplatin-based concurrent chemoradiotherapy( DDP, 100mg/m2,D1,D22 and D43), due to chemoradiotherapy induced toxicity. Combined analyses of NPC-9901 and NPC-9902 Trials indicated that the 5-year locoregional failure free survival was insignificant between the patients received between two and three cycles cisplatin-based concurrent chemoradiotherapy. Our previous studies have also demonstrated that the five years overall survival, distant metastasis free survival and 5-year locoregional failure free survival was not observed significant difference between the patients received between two and three cycles cisplatin-based concurrent chemotherapy. It indicated that one pressing questions remain to be resolved: can we define the optimal dose so that we can reduce toxicity by avoiding unnecessary overdose or an ineffective phase of treatment? Recently, the quantification of pretreatment plasma Epstein-Barr virus (EBV) DNA, which was considered the most potential biomarker to compliment TNM stage, was demonstrated a useful biomarker for the risk stratification, monitoring and prediction of the prognosis of NPC. The investigators previous study demonstrated that for local and regionally advanced NPC patients with EBV DNA <4,000copies/mL, the 3-year's PFS and DMFS was approximate to 90%. Pretreatment plasma EBV DNA levels might be applied to guide concurrent chemotherapy regimen for local and regionally advanced NPC patients. Therefore, the investigators make a hypothesis that the low risk locoregionally advanced NPC patients received two cycles of chemotherapy may gain similar long-term survival as those received three cycles of chemotherapy, leading to less chemotherapy induced toxicity. Therefore, this phase II non-inferiority, randomised controlled clinical trial was designed to assess efficacy for low-risk patients, identified with pretreatment plasma EBV DNA <4,000 copies/mL, received two cycle cisplatin-based chemotherapy compared with three cycle cisplatin-based chemotherapy
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
- •Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma, including WHO II or III
- •Original clinical staged as T3-4N0-3 M0 or any T、N2-3M0（according to the 7th AJCC edition）
- •No evidence of distant metastasis (M0)
- •Pretreatment Plasm EB Virus DNA<4000copies/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 ≤ 1.5×ULN)
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.
- •Receiving other ways of anti-cancer therapy.
- •Suffered from other malignant tumors (except the cure of basal cell carcinoma or uterine cervical carcinoma in situ) previously.
研究组 & 干预措施
Two cycle CCRT
Concurrent cisplatin(100mg/m2,D1,D22)combine with IMRT
干预措施: Cisplatin combine with IMRT (Drug)
Three cycle CCRT
Concurrent cisplatin(100mg/m2,D1,D22 and D43)combine with IMRT
干预措施: Cisplatin combine with IMRT (Drug)
结局指标
主要结局
Progress-free survival
时间窗: 3 years
Progress-free survival is calculated from the date of randomization to the date of the first progress at any site or death from any cause or censored at the date of the last follow-up
次要结局
- The shor-term toxic effects(3 months)
- Complete Response (CR)(after the completion of the chemoradiotherapy treatment (up to 9 weeks))
- Overall Survival(OS)(3 years)
- Locoregional Relapse-Free Survival(LRRFS)(3 years)
- Distant Metastasis-Free Survival (DMFS)(3 years)
- Cost-effectiveness analysis(3 years)
- The monitoring of plasma EBV DNA(3 years)
- Long-term toxicities(3 years)
研究者
Hai-Qiang Mai,MD,PhD
the vice director of nasopharyngeal carcinoma
Sun Yat-sen University