A Phase II Trial of Induction Chemotherapy Followed by Cisplatin With Low Dose vs. Standard Dose IMRT in Stage III Nasopharyngeal Carcinoma Patients With Pretreatment EBV DNA<4000 Copy/ml
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 215
- 试验地点
- 1
- 主要终点
- PFS(progression free survival)
研究概览
简要总结
To study the 2-year PFS (progression-free survival) of patients with stage III nasopharyngeal carcinoma of pretreatment EBV DNA<4000 copy/ml treated with induction chemotherapy followed by two different doses of intensity-modulated radiation therapy and cisplatin.
详细描述
To explore the 2 year PFS of patients with stage III nasopharyngeal carcinoma of pretreatment EBV DNA<4000 copy/ml treated with induction chemotherapy followed by reduced-dose radiation and cisplatin. The enrolled patients will receive 2 cycles of TPF regimen induction chemotherapy, if radiographic CR/PR and EBV DNA=0 after induction chemotherapy, the patients will be delivered by 60 Gy IMRT combined with 3 cycles of cisplatin concurrent chemotherapy. If radiographic SD/PD or EBV DNA>0 after induction chemotherapy, the patients will receive a total of 70 Gy IMRT combined with 3 cycles of cisplatin concurrent chemotherapy.
The included patients will be treated with 2 cycles of TPF regimen induction chemotherapy and 60Gy IMRT combined with cisplatin concurrent chemotherapy. The TPF regimen is consist of paclitaxel liposome 135mg/m2 d1, cisplatin 25mg/m2d1-d3 and 5-Fu 3750mg/m2 civ120h, with a total of two cycles. Concurrent cisplatin chemotherapy is delivered with dose of 100mg/m2, a total of three cycles. The third cycle of cisplatin concurrent chemotherapy is allowed to be delivered within one week after IMRT finished.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Pathological diagnosis of NPC(WHO II or III).
- •Stage III（8thAJCC/UICC staging system) and pretreatment EBVDNA<4000opies/ml.
- •Aged 18-70 years。
- •ECOG = 0-1。
- •HGB≥90 g/L，WBC≥4×109 /L，PLT≥100×109 /L.
- •ALT,AST<2.5 fold of ULN；TBIL<2.0×ULN。
- •CCR≥60ml/min or Cr<1.5×ULN。
- •Signed informed consent
排除标准
- •WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma.
- •Age <18 or >70years.
- •Treatment with palliative intent.
- •Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer.
- •Pregnancy or lactation.
- •History of previous radiotherapy (except for non-melanomatous skin cancers outside intended RT treatment volume).
- •Prior chemotherapy or surgery (except diagnostic) to primary tumor or nodes.
- •Any severe intercurrent disease, which may bring unacceptable risk or affect the compliance of the trial, for example, unstable cardiac disease requiring treatment, renal disease, chronic hepatitis, diabetes with poor control (fasting plasma glucose >1.5×ULN), and emotional disturbance.
研究组 & 干预措施
Reduced dose group
After 2 cycles of induction chemotherapy with Paclitaxel Liposome, Cisplatin and 5-Fluorouracil, patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 6 weeks (30 fractions). Patients also receive cisplatin once per three week for 3 cycles.
干预措施: Intensity-modulated radiation therapy (Radiation)
Reduced dose group
After 2 cycles of induction chemotherapy with Paclitaxel Liposome, Cisplatin and 5-Fluorouracil, patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 6 weeks (30 fractions). Patients also receive cisplatin once per three week for 3 cycles.
干预措施: Paclitaxel liposome (Drug)
Reduced dose group
After 2 cycles of induction chemotherapy with Paclitaxel Liposome, Cisplatin and 5-Fluorouracil, patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 6 weeks (30 fractions). Patients also receive cisplatin once per three week for 3 cycles.
干预措施: Cisplatin (Drug)
Reduced dose group
After 2 cycles of induction chemotherapy with Paclitaxel Liposome, Cisplatin and 5-Fluorouracil, patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 6 weeks (30 fractions). Patients also receive cisplatin once per three week for 3 cycles.
干预措施: 5-Fluorouracil (Drug)
Standard dose group
After 2 cycles of induction chemotherapy with Paclitaxel Liposome,Cisplatin and 5-Fluorouracil, patients undergo standard-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 6 weeks (33 fractions). Patients also receive cisplatin once per three week for 3 cycles.
干预措施: Intensity-modulated radiation therapy (Radiation)
Standard dose group
After 2 cycles of induction chemotherapy with Paclitaxel Liposome,Cisplatin and 5-Fluorouracil, patients undergo standard-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 6 weeks (33 fractions). Patients also receive cisplatin once per three week for 3 cycles.
干预措施: Paclitaxel liposome (Drug)
Standard dose group
After 2 cycles of induction chemotherapy with Paclitaxel Liposome,Cisplatin and 5-Fluorouracil, patients undergo standard-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 6 weeks (33 fractions). Patients also receive cisplatin once per three week for 3 cycles.
干预措施: Cisplatin (Drug)
Standard dose group
After 2 cycles of induction chemotherapy with Paclitaxel Liposome,Cisplatin and 5-Fluorouracil, patients undergo standard-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 6 weeks (33 fractions). Patients also receive cisplatin once per three week for 3 cycles.
干预措施: 5-Fluorouracil (Drug)
结局指标
主要结局
PFS(progression free survival)
时间窗: 2 years
Defined from date of registration to date of first documentation of progression and/or distant metastasis,or death due to any cause. The primary study population for this endpoint is patients who were confirmed post-induction CR /PR and EBV DNA=0 and subsequently received 60Gy radiation therapy.
次要结局
- Overall response rate(2 years)
- Incidence of acute toxicity(2 years)
- Locoregional relapse-free survival(LRFS)(2 years)
- Overall Survival(OS)(2 years)
- Incidence of late toxicity(2 years)
- Change of ADC( apparent diffusion coefficient ) value of DWI(Diffusion-Weighted MRI) of patients predictive of failure(2 years)
- Change of QoL(1 years)
- Change of EORTC quality of life questionnaire(QLQ) Head and Neck score(1 years)
- Plasma EBV DNA copy number(2 years)
- Distant metastasis-free survival(DMFS)(2 years)
研究者
Hai-Qiang Mai,MD,PhD
Professor
Sun Yat-sen University