Nab-paclitaxel Plus Cisplatin and Capecitabine as Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiation for Locoregionally Advanced Nasopharyngeal Carcinoma: a Phase I Dose-escalation Study
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
研究概览
简要总结
Neoadjuvant chemotherapy followed by concurrent chemoradiation (CCRT) has been recommended in the treatment of locoregionally-advanced nasopharyngeal carcinoma (NPC), with docetaxel, cisplatin (DDP) and 5-fluorouracil (5-Fu) shown to be an effective regimen. Capecitabine is the precursor drug of 5-fluorouracil, and has been used in replace of 5-fluorouracil in NPC patients. Nab-paclitaxel (Nab-PTX) is a novel albumin-bound paclitaxel with a superior therapeutic index to docetaxel. We sought to find out the efficacy of Nab-PTX in three-drug triplet (Nab-PTX, DDP and capecitabine) and decide the best administration dose of Nab-PTX.
详细描述
Neoadjuvant chemotherapy followed by concurrent chemoradiation (CCRT) has been recommended in the treatment of locoregionally-advanced nasopharyngeal carcinoma (NPC), with docetaxel, cisplatin (DDP) and 5-fluorouracil (5-Fu) shown to be an effective regimen. Capecitabine is the precursor drug of 5-fluorouracil, and has been used in replace of 5-fluorouracil in NPC patients. Nab-paclitaxel (Nab-PTX) is a novel albumin-bound paclitaxel with a superior therapeutic index to docetaxel. It was developed to reduce toxicities associated with paclitaxel whilst maintaining or improving its chemotherapeutic effect. In vivo preclinical experiments have shown greater volume of distribution of nab-paclitaxel than paclitaxel, with similar half-life and clearance. The efficacy and optimal dose of Nab-PTX combined with DDP as doublet has been explored in metastatic NPC patients and locoregionally advanced patients, and it showed encouraging anti-tumor effects and manageable toxicities. However, what is the optimal dose of Nab-PTX and the efficacy of it in three-drug triplet (Nab-PTX, DDP and capecitabine) needs to be discovered. Therefore, this study aims to evaluate the efficacy and safety of Nab-PTX plus cisplatin and capecitabine neoadjuvant chemotherapy, followed by cisplatin-based concurrent chemoradiotherapy in the patients with locoregionally advanced nasopharyngeal carcinoma, to provide new evidence for the use of Nab-PTX in NPC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 III-IVa （according to the 8th AJCC edition).
- •No evidence of distant metastasis (M0).
- •Male and no pregnant female.
- •Satisfactory performance status: ECOG (Eastern Cooperative OncologyGroup) scale 0-
- •WBC ≥ 4×109 /L and PLT ≥100×109 /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.
- •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
TPX neoadjuvant chemotherapy +CCRT
Patients receive neoadjuvant chemotherapy with Nab-PTX (150/175/200/225/250 mg/m2, D1) , cisplatin (75 mg/m2, D1) and capecitabine (1000 mg/m2, BID, D1-14) every three weeks for three cycles before radiotherapy, then followed by concurrent IMRT and cisplatin (100 mg/m2) concurrent every three weeks during radiotherapy (D1, D22, D43 of RT)
干预措施: Nab paclitaxel (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
时间窗: At the end of each cycle (each cycle is 21 days)
Incidence rate of adverse events (AEs), evaluated on basis of Common Terminology Criteria for Adverse Events (CTCAE) 5.0 criteria.
Maximum tolerated dose
时间窗: At the end of each cycle (each cycle is 21 days)
If more than one-third of patients in a given cohort experienced a dose-limiting toxicity (DLT), enrollment will be stopped and the dose used in the previous cohort will be designated as the maximum tolerated dose
次要结局
- Disease control rate(3 months)
- Overall survival(2-year)
- Objective response rate(3 months)
- Progression-free survival(2-year)
研究者
Hai-Qiang Mai,MD,PhD
Director of the Department of Nasopharyngeal Carcinoma
Sun Yat-sen University