A Randomized, Open-label, Multiple-centre Study of Intercalating and Maintenance Gefitinib in Combination With Chemotherapy for Advanced NSCLC With EGFR Mutation Positive
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 61
- 试验地点
- 1
- 主要终点
- Progression free survival - PFS
研究概览
简要总结
Study Title:
Intercalating and maintenance Gefitinib in combination with chemotherapy (gemcitabine plus carboplatin) as first-line treatment for patients with advanced EGFR mutation-positive non-small cell lung cancer: A randomized, open-label, multiple-centre study.
Target population-Treatment naive EGFR mutant-positive advanced NSCLC patients.
Study Objectives - Primary Study Objective: To investigate whether intercalating and maintenance Gefitinib in combination with chemotherapy improve the Progression-Free Survival (PFS) vs. Gefitinib alone in advanced NSCLC with EGFR activating mutation.
- Secondary Study Objective： To evaluate whether intercalating and maintenance Gefitinib in combination with chemotherapy improve the Objective Response Rate (ORR), Disease control rate (DCR), Overall survival (OS), 2-year OS rate, QOL vs. Gefitinib alone.
Evaluation the safety of Intercalating and Maintenance Gefitinib in combination with chemotherapy.
- Exploratory objective: PFS of arm A vs. PFS 1 + PFS 2 of arm B Dynamic biomarker analysis using blood sample
a: The PFS 1 of arm B is the time from randomization to disease progression of 1st-line therapy or death from any cause, whichever occurs first. The PFS 2 of arm B is the time from the time of PFS 1 to disease progression of 2nd-line therapy or death from any cause, whichever occurs first.
Study Design-Prospective, open-label, randomized, multi-center study.
详细描述
Study Design:
It is a two-arm, prospective, randomized, open-label, multi-center study. The study will be conducted at 5 study sites in China. West China Hospital serves as the lead site for the study. A total of 146 treatments naive EGFR mutant positive advanced NSCLC patients are planned to be enrolled into this study.
There are four periods in this study: baseline period (≤28days),main phase of treatment (Week 0-Week 16 or until disease progression),post-treatment period and follow-up until about 24 months after the last patients enrolment.
- Baseline period: Subject will be enrolled in the study after signing informed consent form (ICF). Investigator will record patient-reported outcome, demographic data and medical history, collect the histological or cytological samples for genetic testing, conduct laboratory examination and perform imaging examination and so on. Notes: The time of imagination is effective within 4 weeks before treatment. The result of haematology, biochemistry and physical examination is effective within 7 days before treatment. Collecting blood one time at screening period (The SOP of blood collection, storage and transportation is in attachment 1).
- Main phase of treatment: There are 8 visits during the main phase of treatment study. During the main phase of treatment, investigator conduct laboratory examination, perform imaging examination, assess the tumor status, and evaluate the patient-reported outcome and safety.
Collecting blood one time every two cycles (The SOP of blood collection, storage and transportation is in attachment 1). 3. Post-treatment period:
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
- •Subjects enrolled in this study are required to meet the following inclusion criteria:
- •Patients between 18 and 75 years of age.
- •Patients with histologically or cytologically diagnosed NSCLC,or patients with recurrent advanced NSCLC after surgery.
- •Harboring activating mutation of EGFR,only including an exon 19 deletion or an exon 21 point mutation.
- •Has at least one measureable lesion by RECIST 1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •No prior systemic chemotherapy or targeted therapy for lung cancer before screening except neoadjuvant or adjuvant patients.
- •Adequate organ function, including the following:
- •Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥1.5 × 109/L,platelets ≥100 × 109/L,and hemoglobin ≥9 g/dL.
- •Hepatic: bilirubin ≤1.5 times the upper limit of normal (× ULN),alkaline phosphatase (AP),aspartate transaminase (AST),and alanine transaminase (ALT) ≤3.0 × ULN (AP,AST and ALT ≤5 × ULN is acceptable if the liver has tumor involvement).
- •Renal: calculated creatinine clearance (CrCl) ≥45 mL/minute based on the standard Cockcroft and Gault formula.
- •Prior radiation therapy allowed to <25% of the bone marrow. Prior radiation to the whole pelvis is not allowed. Prior radiotherapy must be completed at least 4 weeks before study enrolment.
- •Signed informed consent document on file.
- •Estimated life expectancy of ≥12 weeks.
- •Patient compliance and geographic proximity that allow adequate follow up.
排除标准
- •Subjects meeting any of the following exclusion criteria are not to be enrolled in the study.
- •Known severe hypersensitivity to gefitinib.
- •Known brain metastasis unless asymptomatic brain metastasis(without neurotic symptoms and sign) and treated with surgery and/or radiation and stable without steroid treatment for at least 2 weeks prior to the first dose of study medication.
- •Pleural effusion or pericardiac effusion that cannot be controlled by drainage or other procedures.
- •Previous treatment with agents targeting the HER axis.
- •Previous systemic antitumour treatment.
- •The last regimen of neoadjuvant or adjuvant treatment for non-metastatic disease within 12 months of study treatment.
- •EGFR Resistance mutation (+).
- •Surgery undertaken less than 4 weeks before the study.
- •Inability to comply with protocol or study procedures.
- •A serious concomitant systemic disorder that,in the opinion of the investigator，would compromise the patient's ability to complete the study.
- •A serious cardiac condition,such as myocardial infarction within 6 months,angina,or heart disease.
- •Second primary malignancy that is clinically detectable at the time of consideration for study enrolment.
- •Past medical history of Interstitial Lung Disease(ILD),drug induced interstitial disease,radiation pneumonitis which required steroid treatment,or any evidence of clinically active ILD.
- •Pre-existing idiopathic pulmonary fibrosis evidence by CT scan at baseline.
- •Unwillingness to use contraception during the study, women who were pregnant or lactating.
- •Being or planing to participate in other studies.
研究组 & 干预措施
Arm A
Four cycles gemcitabine(d1,8 ) + carboplatin (d1) + gefitinib (15-25), gefitinib 250mg/d from d15 of last cycle until disease progression.
Gemcitabine=1000mg/m2;Carboplatin 5×AUC ; One cycle is 28 days
干预措施: Gefitinib (Drug)
Arm A
Four cycles gemcitabine(d1,8 ) + carboplatin (d1) + gefitinib (15-25), gefitinib 250mg/d from d15 of last cycle until disease progression.
Gemcitabine=1000mg/m2;Carboplatin 5×AUC ; One cycle is 28 days
干预措施: gemcitabine (Drug)
Arm A
Four cycles gemcitabine(d1,8 ) + carboplatin (d1) + gefitinib (15-25), gefitinib 250mg/d from d15 of last cycle until disease progression.
Gemcitabine=1000mg/m2;Carboplatin 5×AUC ; One cycle is 28 days
干预措施: carboplatin (Drug)
Arm B
Gefitinib 250mg/d until disease progression
干预措施: Gefitinib (Drug)
结局指标
主要结局
Progression free survival - PFS
时间窗: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to average 10 months
次要结局
- Overall Survival - OS(the time from randomization to death from any cause,assessed up to 2 years)
- Objective Response Rate - ORR(at day 42 of treatment)
研究者
You Lu
Chief Physician
Sichuan University