A Phase Ⅱ Randomized Clinical Trial Comparing Vinorelbine-ifosfamide With Gefitinib as Third-line Treatment in Advanced EGFR Gene Mutation Negative Non-small Cell Lung Cancer Patients
试验速览
- 阶段
- 2 期
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Progression free survival
研究概览
简要总结
In the National Comprehensive Cancer Network (NCCN) guideline for NSCLC, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is recommended as the third-line treatment for EGFR gene mutation negative NSCLC patients who failed to the first-line platinum doublet chemotherapy [i.e. paclitaxel-carboplatin (PC) or gemcitabine-cisplatin (GP)] and the second-line chemotherapy with docetaxel or pemetrexed. But as we know, if patients had no EGFR gene mutation, EGFR-TKI treatment is not effective. The overall survival is short and the objective response rate is low. As for EGFR gene wild type patients with good performance status, besides EGFR-TKI treatment, other first generation cytotoxic drugs i.e. vinorelbine or ifosfamide maybe an alternative treatment. So the purpose of this clinical trial is to compare the effectiveness and safety of vinorelbine-ifosfamide with gefitinib in advanced or metastatic EGFR gene mutation negative NSCLC patients.
详细描述
Ifosfamide is a first generation cytotoxic drug to treat NSCLC. Phase Ⅱ studies demonstrated that single-agent ifosfamide administrated by various schedules produces response rates of 15-29%, with media survival times of 5-7 months. Ifosfamide has also been used in various combination regimens to treat NSCLC, including platinum based and non-platinum regimens. But in refractory NSCLC patients platinum and some third generation cytotoxic drugs have been used before. So in this study, ifosfamide is combined with vinorelbine. In previous study, Masters reported the objective response rate was 40% and the median survival duration was 50 weeks, with a 1-year survival rate of 48% with vinorelbine-ifosfamide regimen [Vinorelbine 15 mg/m2 on days 1-3, and ifosfamide 2.0g/m2 on days 1-3 with granulocyte-colony stimulating factor (G-CSF) support]. The dose limiting toxicity (DLT) of this regimen is myelosuppression. In our experience, the regimen of vinorelbine 25mg/m2 d1, d8 and ifosfamide 1.25g/m2 d1-d3 with Mesna uroprotection is safe in Chinese population and the objective response rate is about 7% (data not published).
Gefitinib is the first small molecule inhibitor that has directed activity towards EGFR and has shown appreciable response rates in phase Ⅱ trials of patients with previously treated advanced NSCLC. In the posterior analysis of Iressa Dose Evaluation in Advanced Lung Cancer (IDEAL) and IRESSA Survival Evaluation in Lung Cancer (ISEL) trials, the response rate with gefitinib ranges from 2.6% to 10% in wild-type EGFR gene NSCLC patients.
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
- •age range:18-70 years old
- •life expectancy more than 12 weeks
- •histologically or cytologically confirmed inoperable NSCLC (stage ⅢB/Ⅳ)
- •ineligible for curative radiotherapy
- •no prior radiotherapy for the target lesions
- •Eastern Cooperative Oncology Group (ECOG) performance score of 0-2;
- •prior treatments include first-line platinum doublet chemotherapy i.e. PC or GP and second-line chemotherapy with docetaxel or pemetrexed;
- •No EGFR gene mutation detected by Scorpions-ARMS;
- •at least one bidimensionally measurable or radiographically assessable lesion;
- •adequate bone marrow reserve;
- •adequate hepatic and renal function;
排除标准
- •prior treatments including any of the following drugs:gefitinib,vinorelbine and ifosfamide;
- •additional malignancies;
- •uncontrolled systemic disease;
- •any evidence of clinically active interstitial lung disease;
- •newly diagnosed central nervous system (CNS) metastasis and not treated by radiotherapy or surgery;
- •pregnancy or breast feeding phase;
研究组 & 干预措施
Gefitinib
Gefitinib group Gefitinib (Iressa) 250mg once per day until progression disease or intolerant side effects
干预措施: Gefitinib group (Drug)
Vinorelbine-Ifosfamide
VI group Vinorelbine 25mg/m2 d1,d8;Ifosfamide 1.25g/m2 d1-d3(Usually Ifosfamide 2g d1-d3 with Mesna 400mg 0,4,8hours after Ifosfamide administration for 3 days);every 3 weeks;at least for 2-6 cycles depending on the progression disease or the patient's physical condition
干预措施: Vinorelbine, Ifosfamide, Mesna (Drug)
结局指标
主要结局
Progression free survival
时间窗: up to 52 weeks (about one year)
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks.
次要结局
- Overall survival(Up to 100 weeks)
- objective response rate(up to 9 weeks)
- the score of functional assessment of cancer treatment-lung (FACT-L)(Up to 100 weeks)
- Number of participants with adverse events(Up to six months)