Phase III Study of IV Vinflunine in Combination With Methotrexate Versus Methotrexate Alone in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Previously Treated With Platinum-based Chemotherapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 459
- 试验地点
- 1
- 主要终点
- Overall Survival in the ITT Population (Months)
研究概览
简要总结
For patients relapsing after platinum-based therapy, few data are available. The current use of cetuximab associated with radiotherapy in localized disease and associated with platinum-based chemotherapy in the first-line setting stresses the need for new therapeutic options at later stages of SCCHN.Vinca-alkaloids demonstrated activity in SCCHN. Vinflunine demonstrated superior antitumour activity to vinorelbine in preclinical animal models. Recent preliminary phase I results of the vinflunine plus methotrexate combination in SCCHN, based on a clinical review, show encouraging antitumour activity and an acceptable safety profile. Therefore the combination of vinflunine and methotrexate appears a promising salvage regimen after platinum failure.
The present study has been designed as a multicenter, randomised phase III study which will compare the combination of IV vinflunine with methotrexate to methotrexate alone in SCCHN patients having failed platinum-based therapy.
详细描述
This study was designed to compare the OS of VFL plus MTX versus MTX alone in patients with SCCHN who had failed platinum-based chemotherapy.
The trial was designed in accordance with current standards used routinely in oncology phase III trials and used established methods of assessment. The RECIST (version 1.1) and NCI CTCAE (version 3.0) guidelines are internationally recognised methods for assessing efficacy and tolerance, respectively.
The patient population was appropriate for this type of phase III study and included adult patients with recurrent and/or metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, who had received prior chemotherapy regimens with documented progression. This population of patients was considered appropriate to meet the study objectives.
Recent preliminary phase I results of the VFL plus MTX combination in SCCHN, reported in a clinical review, showed encouraging antitumour activity and an acceptable safety profile A number of chemotherapy agents have been reported as having single-agent activity in SCCHN. However, reliable evidence of efficacy in the second-line setting is lacking, and there is currently no established standard of care. MTX used alone as the reference regimen at a dose of 40 mg/m2/week can be considered as the best available evidence-based option. Also, other trials using this comparator have demonstrated that it is generally accepted as a reasonable choice, and is often used in general practice.
The efficacy and safety assessments employed in this study are standard measures routinely used in studies of this type
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed recurrent and/or metastatic squamous cell carcinoma
- •Documented progressive disease after chemotherapy for locoregionally advanced or recurrent/metastatic SCCHN which included a platinum derivative
- •Measurable or non measurable disease
- •adequate haematological, hepatic and renal functions
- •WHO performance status < 1
排除标准
- •Nasopharyngeal carcinoma
- •History of brain or leptomeningeal involvement
- •Albumin level < 35 g/L
- •Patients with weight loss ≥ 5% within the last 3 months
- •Grade > 2 peripheral neuropathy at study entry
- •"Third space" fluids (pleural effusion, ascites, massive edema)
- •Prior treatment with vinca-alkaloids and methotrexate
研究组 & 干预措施
Vinflunine plus methotrexate
vinflunine IV 280 mg/m² Day 1 plus methotrexate IV 30 mg/m² Day 1 and Day 8 every 3 weeks
干预措施: Vinflunine (Drug)
Methotrexate
methotrexate IV 40 mg/m² Day 1, 8 and 15 every 3 weeks
干预措施: Methotrexate (Drug)
结局指标
主要结局
Overall Survival in the ITT Population (Months)
时间窗: Participants will be followed till death (if they are not lost for follow-up), an expected average of 7.5 months
Time from randomization to the date of death or last follow-up. The survival duration of patients still alive, was censored at the date of last contact or last follow-up.
次要结局
- Progression Free Survival(an expected average of 4 months)
- Disease Control Rate(30 months)
- Duration of Response(30 months)
- Objective Response Rate (ORR)(6 weeks)