A Randomized, Controlled, Open-label, Prospective Trial of S-1 Plus Gefitinib Versus Gefitinib Monotherapy for First-line Treatment of Advanced Non-squamous Non-small Cell Lung Cancer With EGFR-sensitive Mutation
试验速览
- 阶段
- 2 期
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Progression free survival(PFS)
研究概览
简要总结
To investigate the survival benefit of first-line therapy for patients with EGFR-sensitive mutation-positive advanced non-squamous non-small cell lung cancer treated with S-1plus gefitinib versus gefitinib monotherapy
详细描述
This is a randomized, controlled, open-plan, prospective clinical study. According to the available evidence, we selected patients with locally advanced or metastatic non-squamous non-small cell lung cancer with stage Ⅲ-C-Ⅳ confirmed by cytology or histology and positive EGFR-sensitive mutation, then patients accept first-line treatment with S-1 plus gefitinib or gefitinib. This study will collect FFS during treatment until the patient dies and will follow the survival of the subject after the disease progresses.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Volunteered for attending the study, and signed informed consent form (ICF)to participate in the study.
- •Males or females aged ≥18 years, < 75 years.
- •Cytologically and Histologically documented, advanced or recurrent (stage IIIc-IV) non-small cell lung cancer patients .
- •exon 19 deletion or exon 21 L858R for EGFR mutation.
- •Patients hadn't received past system treatment, including cytotoxic drugs; For patients who have received adjuvant or neoadjuvant chemotherapy appears recurrence or metastasis more than 6 months from accepting the last dose of chemotherapy drugs
- •Patients must have at least 1 measurable lesion according to the RECIST (version 1.1) criteria.
- •Life expectancy ≥12 weeks.
- •ECOG performance status 0-
- •Adequate organ function as defined by the following criteria:
- •Absolute neutrophil count (ANC) ≥1.5 x 109/L, and Platelet count ≥100 x 109/L, and Hemoglobin ≥9 g/dL (may be transfused to maintain or exceed this level).
- •Total bilirubin ≤ 1.5 x upper limit of normal (ULN), alkaline phosphatase (AP), Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN in the absence of liver metastases or up to 5 ULN in case of liver metastases.
- •creatinine clearance≥ 60 ml/min.
- •Fertile men and women must use effective contraception.
- •Subjects are allowed to receive radiation for lesions other than the target lesion, but the end of radiotherapy should be at least 3 weeks apart from randomization;
- •The investigators should judge the subject's compliance to meet the study requirements.
排除标准
- •Histology confirmed for squamous carcinomas, including mixed gland scale cancer, small cell lung cancer.
- •Patients with prior any anti-tumor therapy,including chemotherapy, radiotherapy, immunotherapy or biotherapy
- •Patients with prior exposure to EGFR-TKIs or 5-Fu
- •Not recovered from previous toxic reactions for anticancer treatment (CTCAE grade 1) or not fully recovered from previous surgery
- •Patients who have brain metastasis. It is permitted if the patient has been treated with surgery and/or radiation with evidence of stable disease for at least 4 weeks.
- •Patients haven't been diagnosed other malignant disease, except the basal cell carcinoma and cervical carcinoma.
- •A uncontrolled clinical infection, activity, including acute pneumonia,HIV,HCV. , etc.
- •Sullivudine, brivudine or other antiviral drugs of similar structure were used within 2 months before randomization
- •Patients who have a difficulty in swallowing or drug absorption.
- •Patients with a history of interstitial lung disease or with interstitial lung disease;
- •There are diseases of alimentary canal such as active duodenal ulcer, the ulcerous colitis, intestinal obstruction or other conditions which can cause gastrointestinal bleeding or perforation in the investigator's opinion; or patient has a history of intestinal perforation, intestinal fistula.
- •Evaluation of cardiac function: left ventricular ejection fraction < 50% (echocardiography); Moderate or above disorders of mitral valve and tricuspid shut down;, serious/unstable angina or acute myocardial infarction coronary artery bypass surgery in 6 months before enrollment; patients with class 2 and above cardiac dysfunction according to New York heart association (NYHA) classification
- •Patients with medical history of hemoptysis (defined as about 2.5ml bright blood) 2 weeks before the enrollments
- •Stroke and transient ischemic in 12 months before enrollment.
- •Severe ulcer in the skin wound, trauma and mucosa or fractures have been not fully healed.
- •Patients received CYP3A4 strong inhibitor and/or inducer in 2 weeks before enrollment; Patients received P-gp and breast cancer resistance protein (BCRP) substrates drug in 2 weeks before enrollment.
- •Patients has participated in other clinical trials of antitumor drugs within the previous 28 days, except for those who were able to prove that they were using placebo;
- •Pregnancy or lactating women or pregnant women may be pregnant before pregnancy test positive;
- •Unwillingness to receive contraception by patients or their sexual partners who are fertile but unwilling to receive contraception;
- •The investigators think that there is any clinical or laboratory abnormalities in the subjects that are not suitable for this study.
- •There is a serious psychological or mental abnormalities, researchers assess subjects to participate in this clinical study compliance is insufficient;
- •Allergic reactions to analogs of gefitinib and S-1 and / or Analogs and / or excipients in test drugs.
研究组 & 干预措施
S-1 plus Gefitinib
S-1: According to the body surface area (BSA) to determine the dose, twice daily, after breakfast and dinner orally, continuous administration of 14 days, rest for 7 days. BSA <1.25 m2, 80 mg / day; BSA 1.25 m2 to <1.5 m2, 100 mg / day; BSA 1.5 m2 or more, 120 mg / day. Until disease progression, intolerance of toxicity or withdrawal of informed consent from the subject.
Gefitinib: 250mg, 1 day, orally, fasting or with the same service. Until disease progression, intolerance of toxicity or withdrawal of informed consent from the subject.
干预措施: S-1 plus Gefitinib (Drug)
Gefitinib
Gefitinib 250 mg/day oral daily
干预措施: Gefitinib (Drug)
结局指标
主要结局
Progression free survival(PFS)
时间窗: 2 years
From start of anti-cancer therapy until progression or death.To evaluate the disease free survival of gefitinib combined with S-1 and gefitinib in patients with Pathological stage IIIc-IV NSCLC harbouring sensitive mutations of EGFR. Progression free survival (PFS)- defined as the time from initial medication to the first documented disease progression or death, whichever occurs first.
次要结局
- Objective response rate(ORR)(2 years)
- Overall survival(OS)(3 years)
- Number of Participants with Adverse Events(3 years)
- Disease control rate(2 years)