A Randomized Placebo-controlled Phase II Study of Intercalated Administration of Pemetrexed/Cisplatin With Iressa® (Gefitinib) or Placebo as First-line Treatment of Stage IIIB/IV Lung Adenocarcinoma in Never-smokers
试验速览
- 阶段
- 2 期
- 入组人数
- 162
- 试验地点
- 1
- 主要终点
- To compare progression-free survival
研究概览
简要总结
Intercalated administration of Iressa® (gefitinib) on days 5-18 of chemotherapy cycle improve the efficacy of Pemetrexed/platinum regimen given as first-line treatment for never-smokers with advanced (stage IIIB/IV) lung adenocarcinoma.
详细描述
Investigators believe this PFS curve crossing-over in both IPASS and First-SIGNAL study is mainly due to early progression of EGFR mutation-negative tumors after gefitinib alone. Taken together with the FASTACT trial results, this PFS curve crossing-over may well be averted if effective chemotherapy is given together with gefitinib in a most optimum timing and sequence. Apparently, timing of EGFR-TKI administration within chemotherapy cycles is very critical, as shown in OSI 9774 trial.
In this placebo-controlled randomized phase II, Investigators propose to give gefitinib on days 5-18 of a 3-weekly chemotherapy cycle of pemetrexed/cisplatin to avoid any potential overlap of EGFR-TKI effects on chemotherapy or vice versa. Investigators would like to generate promising pilot data, which warrants a large phase III trial. Investigators hope to show that intercalated administration of Iressa® (gefitinib) and Pemetrexed/platinum regimen improves the outcome of never-smokers with advanced (stage IIIB/IV) lung adenocarcinoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed diagnosis of adenocarcinoma of lung with or without BAC features; however, adenocarcinoma combined with other histology, such as small cell carcinoma or squamous carcinoma, is not allowed.
- •Stage IIIB (not amenable for radical loco-regional therapy) or stage IV (metastatic) patients according to the 7th TNM staging system
- •Never-smoking defined as not more than 100 cigarettes during the lifetime
- •ECOG performance status of 0-2
- •Good organ function
- •The presence of CNS metastases is not considered as an exclusion criterion, provided that there is good control of the symptoms with corticosteroids
- •Patients must sign an informed consent indicating that they are aware of the investigational nature of the study in keeping with the policy of the hospital. The only approved consent form is attached to this protocol
排除标准
- •Patients with prior exposure to agents directed at the HER
- •Patients with prior chemotherapy or therapy with systemic anti-tumour therapy for advanced disease.
- •Lack of physical integrity of the upper gastrointestinal tract, or malabsorption syndrome, or inability to take oral medication, or have active peptic ulcer disease.
- •Known severe hypersensitivity to gefitinib or to any of the study drugs.
- •Any evidence of clinically active interstitial lung disease
- •Concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or St John's Wort
- •Prior invasive malignancies 3 years prior to study entry except adequately treated cutaneous basal cell carcinoma or uterine cervix in situ cancer
- •As judged by the investigator, any evidence of severe or uncontrolled systemic disease
- •Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the study
- •Treatment with a non-approved or investigational drug within 30 days before Day 1 of study treatment.
- •Pregnancy or breast-feeding (women of child-bearing potential).
- •Sexually active males and females (of childbearing potential) unwilling to practice acceptable methods of birth control
研究组 & 干预措施
Study arm
Pemetrexed plus Cisplatin plus Gefitinib
干预措施: Gefitinib (Drug)
Study arm
Pemetrexed plus Cisplatin plus Gefitinib
干预措施: Pemetrexed plusCIsplatin (Drug)
Placebo arm
Pemetrexed plus Cisplatin plus Placebo
干预措施: Placebo (Drug)
Placebo arm
Pemetrexed plus Cisplatin plus Placebo
干预措施: Pemetrexed plusCIsplatin (Drug)
结局指标
主要结局
To compare progression-free survival
时间窗: minimum 1-year follow-up
from date of randomization until the date of first documented progression or death from any case. Assessed minimum 1 years.
次要结局
- To compare objective response rate (CR+PR)(minimum 1-year follow-up)
- To compare duration of response.(minimum 1-year follow-up)
- To compare non progression rate (CR+PR+SD) at 16 weeks.(at 16 weeks)
- To compare overall survival.(minimum 1-year follow-up)
- To compare number of Grade 3/4 Adverse Events(average up to 1 year)
- To assess biomarker(minimum 1-year follow-up)
研究者
Jin Soo Lee
Principal Investigator
National Cancer Center, Korea