A Phase Ⅱ Randomized Controlled Trial to Compare Chemotherapy Sequenced by EGFR-TKIs and Chemotherapy Combined With EGFR-TKIs for Advanced or Metastatic NSCLC Patients Failed to EGFR-TKIs Therapy
概览
- 阶段
- 2 期
- 干预措施
- combined group
- 疾病 / 适应症
- Non Small Cell Lung Cancer
- 发起方
- Peking Union Medical College Hospital
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- progression free survival
- 最后更新
- 13年前
概览
简要总结
There are two different treatment modes for NSCLC patients who failed to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) after initially responding to EGFR-TKI. One is EGFR-TKI combined with chemotherapy and the other is chemotherapy followed by EGFR-TKI. It is unclear which one is more suitable to this group of lung cancer patients. So this phase Ⅱclinical trial is designed to compare the efficiency and safety of these two different treatment modes.
详细描述
Responses to EGFR-TKIs are quiet dramatic and durable, especially in patients with EGFR gene classic mutations, such as 19 deletion or 21 leucine 858 arginine(L858R). However, most patients with NSCLC who respond to EGFR-TKIs eventually experience progression of disease after approximately 12 months. The lack of an established therapeutic option for NSCLC patients who have progressive disease after EGFR-TKIs failure poses a great challenge to physicians in terms of how best to manage this growing group of lung cancer patients. In clinical practice some of the initially EGFR-TKI sensitive tumors which progressed evidence a striking increase in tumor volume within several weeks, after being taken off EGFR-TKI. This response is called "rebound phenomenon". Most experts still believe that these tumors continue to be "oncogene-addicted" to EGFR. So it is rational that EGFR-TKI combined with another chemotherapy regimen can be used to treat NSCLC after the failure of EGFR-TKI therapy. However in some phase Ⅱclinical trials involved a few NSCLC patients who failed to EGFR-TKI therapy, another treatment mode, that is to say, at least one cytotoxic chemotherapy was used firstly then switched to EGFR-TKI therapy until progression of disease, was used and called reintroduction or retreatment of EGFR-TKI. Using this treatment mode, some investigators reported the partial remission (PR) and disease control rate (DCR) were observed in 21.7%-36% and 65.2%-86% NSCLC patients.
研究者
入排标准
入选标准
- •age ≥ 18 years
- •histologically and cytologically proven non-small cell bronchogenic carcinoma (sputum cytology alone was not acceptable)
- •clinical stages ⅢB or Ⅳ
- •recurrent or refractory disease following previous first-line chemotherapy regimens containing platinum and second-line EGFR-TKIs therapy
- •partial remission (PR) or stable disease (SD) at least for 6 months during previous EGFR-TKI treatment
- •at least one bidimensionally measurable or radiographically assessable lesion
- •Eastern cooperative oncology group performance status (ECOG PS) ≤ 2
- •life expectancy ≥ 12 weeks
- •adequate hematological, renal, and hepatic functions
排除标准
- •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
combined group
combined group chemotherapy with docetaxel 75mg/m2 d1 or pemetrexed 500mg/m2 d1, every 3 weeks,at least 2 cycles and the maximal cycle is 6 depending on disease evaluation and patient's physical condition combined with gefitinib 250mg once per day from the start day of chemotherapy until disease progression or intolerable side effects.
干预措施: combined group
sequenced group
sequenced group chemotherapy with docetaxel 75mg/m2 d1 or pemetrexed 500mg/m2 d1, every 3 weeks,at least 2 cycles and the maximal cycles is 6 depending on disease evaluation or patient's physical condition sequenced by gefitinib 250mg once per day until disease progression or intolerable side effects.
干预措施: Sequenced group
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 100weeks)
- Number of participants with adverse events(Participants will be followed for the duration of treatment, an expected average of 52 weeks.)