A Multi-institutional, Randomized Controlled, Phase II Clinical Trial on Comparison of Efficacy and Safety of Nedaplatin Plus 5-Fu Combined With and Without Endostar® Continuous Intravenous Infusion in Refractory Nasopharyngeal Carcinoma
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 328
- 试验地点
- 1
- 主要终点
- objective response (OR) rate based on Recist 1.1 edition
研究概览
简要总结
We define refractory nasopharyngeal carcinoma as the following: recurrence with radiation brain injury after radiotherapy, recurrence after the second or more courses of radiotherapy, standard treatment failure after recurrence, and first-line treatment failure after multiple distant metastasis.
There is no standard treatment for refractory nasopharyngeal carcinoma. Platinum plus 5-Fu is the classic regimen for primary treatment of nasopharyngeal carcinoma.
Endostatin is a multiple targeted angiogenesis inhibitor acting on tumor associated neovascular endothelial cells, normalizing the morphology and function of tumor vasculature, and indirectly leading to the quiescence or reduction of tumors.
The purpose of this phase II clinical trial is to determine the efficacy and safety of nedaplatin plus continuous low dose 5-Fu intravenous infusion combined with endostar® (Recombinant Human Endostatin Injection) continuous intravenous infusion compared with nedaplatin plus continuous low dose 5-Fu intravenous infusion alone in refractory nasopharyngeal carcinoma.
The study hypothesis is that nedaplatin plus continuous low dose 5-Fu intravenous infusion combined with endostar® continuous intravenous infusion is effective and safe in refractory nasopharyngeal carcinoma.
详细描述
With the extension of survival time in nasopharyngeal carcinoma(NPC), more and more patients suffer from recurrence with radiation brain injury after radiotherapy, recurrence after the second or more courses of radiotherapy, standard treatment failure after recurrence, and first-line treatment failure after multiple distant metastasis. We define these four types as refractory nasopharyngeal carcinoma[1-2] due to the complex and high risk of treatment and poor prognosis. For recurrence and metastasis NPC, the objective response rate ranges from 25% to 46.4% with platinum-based, or 5-Fu-based, or gemcitabine-based salvage chemotherapy[2--5].
At present, there is no standard treatment for refractory nasopharyngeal carcinoma.
Most patients in this trial were pretreated with cisplatin-based chemotherapy. Nedaplatin has the equivalent antitumor effect with cisplatin and less renal toxicity and gastrointestinal toxicity in the treatment of NPC[6]. In addition, nedaplatin does not have the cross tolerance with cisplatin. After cisplatin failure, nedaplatin(80-100 mg/m2) still work in NPC treatment[3].
5-Fu is a classic, effective, and safe chemotherapeutic drug in NPC treatment. Low dose continuous intravenous infusion of 5-Fu(300mg/m2/d, 6 weeks) is a effective regimen for recurrent and metastasis NPC with low toxicity[4].
Endostatin is a multiple targeted angiogenesis inhibitor acting on tumor associated neovascular endothelial cells, normalizing the morphology and function of tumor vasculature, and indirectly leading to the quiescence or reduction of tumors[7-9]. Anti-angiogenic therapy might optimally require that endothelial cells be exposed to steady blood levels of the inhibitor, and blood levels of certain angiogenesis inhibitors (such as endostatin) that are too high or too low will be ineffective[7,10]. Endostar® is recombinant human endostatin injection with better medicinal properties, stability and curative effect. Hoekman K. etc conducted a phase I clinical pharmacokinetic study in advanced cancer and the results showed that continuous intravenous pump of endostar® is safe[11]. Moreover, endostar® combined with chemotherapy can improve the outcome of the chemotherapy alone and does not increase the treatment related toxicity, such as in advanced non-small-cell lung cancer[12], advanced cervical cancer[13], advanced gastric cancer[14] and also metastasis NPC[15].
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 have provided a signed Informed Consent Form.
- •Histologically confirmed diagnosis of refractory nasopharyngeal carcinoma (the best), or when histology is difficult to obtained, the following clinical diagnosis of refractory nasopharyngeal carcinoma must be confirmed: clear and directional clinical symptoms, at least two kinds of imaging diagnosis on the basis of magnetic resonance (MR), and clear and directional signs.
- •Age: 18-70 years old.
- •Without dysfunction of heart, lung, liver, kidney, and hematopoiesis, and normal electrocardiogram.
- •Karnofsky Performance Scores ≥ 50, Life expectancy ≥ 3 months, tolerance to at least two cycles of chemotherapy.
- •At least one measurable tumor based on RECIST 1.1 ( longest diameter: ≥20 mm by CT or magnetic resonance (MR) scan)
- •No history of serious allergic to biologic agents
- •No history of other malignant tumors, except cured cervical carcinoma in situ and basal skin cancer.
排除标准
- •Having the serious cardiovascular disease or other serious complications.
- •Woman in pregnancy and breast-feeding.
- •Allergic to intervention drugs and dextran.
- •Patients participated in clinical trials of other drugs within 4 weeks.
- •Use of other chemotherapy drugs, biological treatment, and Chinese medicine anti-cancer drugs at the same time.
研究组 & 干预措施
Nedaplatin+5-Fu+Endostar
Drug: Recombinant Human Endostatin Injection (Endostar) Endostar, 15mg/m2/d, continuous intravenous infusion in 2ml/h for 30 days each cycle, 60 days as one cycle, 6 cycles in total Drug: Fluorouracil (5-Fu) 5-Fu, 200mg/m2/d, continuous intravenous infusion in 2ml/h for 30 days each cycle, 60 days as one cycle, 6 cycles in total Drug: Nedaplatin Nedaplatin, 80mg/m2/d, intravenous drip on d1 and d28 each cycle, 60 days as one cycle, 6 cycles in total
干预措施: Recombinant Human Endostatin Injection (Endostar) (Drug)
Nedaplatin+5-Fu+Endostar
Drug: Recombinant Human Endostatin Injection (Endostar) Endostar, 15mg/m2/d, continuous intravenous infusion in 2ml/h for 30 days each cycle, 60 days as one cycle, 6 cycles in total Drug: Fluorouracil (5-Fu) 5-Fu, 200mg/m2/d, continuous intravenous infusion in 2ml/h for 30 days each cycle, 60 days as one cycle, 6 cycles in total Drug: Nedaplatin Nedaplatin, 80mg/m2/d, intravenous drip on d1 and d28 each cycle, 60 days as one cycle, 6 cycles in total
干预措施: Fluorouracil (5-Fu) (Drug)
Nedaplatin+5-Fu+Endostar
Drug: Recombinant Human Endostatin Injection (Endostar) Endostar, 15mg/m2/d, continuous intravenous infusion in 2ml/h for 30 days each cycle, 60 days as one cycle, 6 cycles in total Drug: Fluorouracil (5-Fu) 5-Fu, 200mg/m2/d, continuous intravenous infusion in 2ml/h for 30 days each cycle, 60 days as one cycle, 6 cycles in total Drug: Nedaplatin Nedaplatin, 80mg/m2/d, intravenous drip on d1 and d28 each cycle, 60 days as one cycle, 6 cycles in total
干预措施: Nedaplatin (Drug)
Nedaplatin+5-Fu
Drug: Fluorouracil (5-Fu) 5-Fu, 200mg/m2/d, continuous intravenous infusion in 2ml/h for 30 days each cycle, 60 days as one cycle, 6 cycles in total Drug: Nedaplatin Nedaplatin, 80mg/m2/d, intravenous drip on d1 and d28 each cycle, 60 days as one cycle, 6 cycles in total
干预措施: Fluorouracil (5-Fu) (Drug)
Nedaplatin+5-Fu
Drug: Fluorouracil (5-Fu) 5-Fu, 200mg/m2/d, continuous intravenous infusion in 2ml/h for 30 days each cycle, 60 days as one cycle, 6 cycles in total Drug: Nedaplatin Nedaplatin, 80mg/m2/d, intravenous drip on d1 and d28 each cycle, 60 days as one cycle, 6 cycles in total
干预措施: Nedaplatin (Drug)
结局指标
主要结局
objective response (OR) rate based on Recist 1.1 edition
时间窗: From the date of first drug administration, evaluation of response was performed every cycle during the treatment and then every 3 months after the completion of the treatment up to 36 months
include complete remission and partial remission
次要结局
- Overall Survival (OS)(From the date of first drug administration until the date of death, assessed up to 36 months)
- Number of participants with adverse events (AEs) and serious adverse events (SAEs)(From the date of first drug administration, evaluation was performed every cycle during the treatment and then every 3 months after the completion of the treatment up to 36 months, using NCI CTCAE version 4.0)
- Quality of life(From the date of first drug administration, evaluation was performed every cycle during the treatment and then every 3 months after the completion of the treatment up to 36 months, using EORTC quality of life questionnaire (QLQ)-C30)
- Disease Control Rate (DCR)(From the date of first drug administration, evaluation of response was performed every cycle during the treatment and then every 3 months after the completion of the treatment up to 36 months)
- Progress Free Survival (PFS)(From the date of first drug administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months)
研究者
Yun-fei Xia
Department of Radiation Oncology, Sun Yat-Sen University Cancer Center
Sun Yat-sen University