Randomized Phase II Trial of Concurrent Chemoradiotherapy with or Without Nimotuzumab for High Risk Nasopharyngeal Carcinoma After Induction Chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 246
- 试验地点
- 1
- 主要终点
- Progress-free survival (PFS)
研究概览
简要总结
This is the first phase II randomized clinical trial of concurrent chemoradiotherapy with or without EGFR blocker Nimotuzumab for high risk advanced nasopharyngeal carcinoma(NPC) , determining whether concurrent chemoradiotherapy(CCRT) combined with nimotuzumab can improve the survival rate of high-risk patients and may provide new evidence for individualized comprehensive treatment of locally advanced NPC.
详细描述
Currently, although NCCN(National Comprehensive Cancer Network) guidelines recommend induction chemotherapy combined with concurrent chemoradiotherapy as IIA level-evidenced treatment for locally advanced nasopharyngeal carcinoma (stage II-IVa),there is still about 20-30% of patients with locally advanced nasopharyngeal carcinoma experienced recurrence and metastasis after radical treatment.
Our previous results showed that patients with plasma Epstein-Barr virus(EBV) DNA> 0 copy/mL or stable disease/progressive disease(SD/PD) after induction chemotherapy had a significantly higher risk of disease progression than patients with plasma EBV DNA=0 copy/mL and complete response/partial response(CR/PR),according to Response Evaluation Criteria in Solid Tumors (RECIST). As for these high-risk patients, the urgent clinical problem to be solved is whether increased treatment intensity during concurrent chemoradiotherapy can improve their survival rates.
Epidermal growth factor (EGFR) is an important therapeutic target for nasopharyngeal carcinoma.Multiple retrospective studies have shown that chemoradiotherapy combined with the EGFR blocker nimotuzumab improved the survival rate of patients with locally advanced nasopharyngeal carcinoma compared with chemoradiotherapy alone. However, phase II randomized clinical trial about the incorporation of nimotuzumab into concurrent chemoradiotherapy is still limited.
This is the first phase II randomized clinical trial of concurrent chemoradiotherapy with or without Nimotuzumab for high risk locally advanced NPC patients, determining whether concurrent chemoradiotherapy combined with nimotuzumab can improve the survival rate of high-risk patients and may provide new evidence for individualized comprehensive treatment of locally advanced nasopharyngeal carcinoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Parallel
- 主要目的
- Prevention
- 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
- •Age 18-70, regardless of sex.
- •Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma with positive EGFR expression, type of WHO II or III, clinical stage II-IVa (according to the 8th American Joint Committee on Cancer[AJCC] edition)
- •Patients with plasma EBV DNA> 0 copy/mL or SD/PD according to RECIST after two cycle induction chemotherapy
- •ECOG (Eastern Cooperative Oncology Group) score: 0-1
- •Women in their reproductive years should ensure that they use contraception during the study period.
- •Hemoglobin (HGB) ≥90 g/L, white blood cell (WBC) ≥4×109 /L, platelet (PLT) ≥100×109 /L.
- •Liver function: Alanine transaminase(ALT), Aspartate aminotransferase(AST)< 2.5 times the upper limit of normal value (ULN), total bilirubin <2.0×ULN.
- •Renal function: serum creatinine <1.5×ULN
- •Patients must sign informed consent and be willing and able to comply with the requirements of visits, treatment, laboratory tests and other research requirements stipulated in the research schedule;
排除标准
- •Histologically confirmed keratinizing squamous cell carcinoma (WHO I)
- •Receiving radiotherapy or chemotherapy or targeted therapy previously
- •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 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.
研究组 & 干预措施
CCRT + Nimotuzumab
Patients whose plasma EBV DNA> 0 copy/mL or SD/PD according to RECIST after two cycle induction chemotherapy( TPF :Paclitaxel liposome135mg/m2 d1+DDP 25mg/m2 d1-d3+ 5-fu 750mg /m2/day civ120h, every 3 weeks for 2 courses) will have concurrent cisplatin (100mg/m2, every three weeks,D1,D22,D43 of intensity modulated radiotherapy) + nimotuzumab (200mg, once a week during radiotherapy, a total of 7 weeks)
干预措施: CCRT+Nimotuzumab (Drug)
CCRT alone
Patients whose plasma EBV DNA> 0 copy/mL or SD/PD according to RECIST after two cycle induction chemotherapy( TPF :Paclitaxel liposome135mg/m2 d1+DDP 25mg/m2 d1-d3+ 5-fu 5-fu 750mg /m2/day civ120h, every 3 weeks for 2 courses) will have concurrent cisplatin (100mg/m2, every three weeks,D1,D22,D43 of intensity modulated radiotherapy) )
干预措施: CCRT alone (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
次要结局
- Incidence rate of adverse events (AEs)(2 years)
- Locoregional Relapse-Free Survival (LRFS)(2 years)
- Distant Metastasis-Free Survival (DMFS)(2 years)
- Evaluate EGFR expression level and EGFR Gene Copy Number as a predictive marker for survival outcomes(2 years)
- Plasma EBV DNA copy number(2 years)
- Correlation between the frequency of EGFR-specific T cells after treatment and survival outcomes(2 years)
- Objective Response Rate (ORR)(Three months after the completion of the CCRT with or without Nimotuzumab treatment)
- Overall Survival (OS) the last follow-up.(2 years)
研究者
Hai-Qiang Mai,MD,PhD
Deputy Director of the Department of Nasopharyngeal Carcinoma
Sun Yat-sen University