NCT03529084撤回3 期
A Randomized, Open-label, Phase III Study of Single Agent Nazartinib Versus Investigator's Choice (Erlotinib or Gefitinib) as First-Line Treatment in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR Activating Mutations
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 主要终点
- Progression Free Survival (PFS) by Blinded independent review committee (BIRC)
研究概览
简要总结
This is a phase III, open label, randomized controlled multi-center global study designed to evaluate the safety and efficacy of single agent nazartinib (EGF816) compared with investigator's choice (erlotinib or gefitinib) in patients with locally advanced or metastatic NSCLC who are treatment naïve and whose tumors harbor EGFR activating mutations (L858R or ex19del).
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
- Single (Outcomes Assessor)
盲法说明
blinded independent review committee for primary endpoint of PFS
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
- •Written informed consent obtained prior to any screening procedures.
- •Histologically documented locally advanced or metastatic, stage IIIB/ IIIC or stage IV NSCLC with documented EGFR activating mutation (L858R or ex19del)
- •Provision of a tumor tissue sample to allow for retrospective analysis of EGFR mutation status
- •No prior treatment with any systemic antineoplastic therapy in the advanced setting
- •Recovered from all toxicities related to prior treatment
- •Presence of at least one measurable lesion according to RECIST 1.1
- •Eastern Cooperative Oncology Group (ECOG) performance ≤1
- •Meet the following laboratory values at the screening visit:
- •Absolute Neutrophil Count ≥1.5 x 109/L
- •Platelets ≥75 x 109/L
- •Hemoglobin (Hgb) ≥9 g/dL
- •Creatinine Clearance ≥ 45 mL/min using Cockcroft-Gault formula
- •Total bilirubin ≤1.5 x ULN
- •Aspartate transaminase (AST) ≤ 3.0 x ULN, except for patients with liver metastasis, who may only be included if AST ≤5.0 x ULN
- •Alanine transaminase (ALT) ≤ 3.0 x ULN, except for patients with liver metastasis, who may only be included if ALT ≤5.0 x ULN
排除标准
- •Prior treatment with EGFR-TKI.
- •Known T790M positive mutation. Any other known EGFR activating mutations other than L858R or ex19del. Patients whose tumors harbor other EGFR mutations concurrent with L858R or ex19del EGFR mutations are eligible.
- •Symptomatic brain metastases
- •History of interstitial lung disease or interstitial pneumonitis
- •Any medical condition that would, in the investigator's judgment, the patient's in the study due to safety concerns, compliance with clinical study procedures or interpretation of study results
- •Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years..
- •Presence of clinically significant ophthalmologic abnormalities
- •Bullous and exfoliative skin disorders of any grade
- •Presence or history of microangiopathic hemolytic anemia with thrombocytopenia.
- •Known history of testing positive for human immunodeficiency virus (HIV) infection
- •Cardiac or cardiac repolarization abnormality
- •Major surgery: ≤4 weeks to starting study treatment or who have not recovered from side effects of such procedure.
- •Unable or unwilling to swallow tablets or capsules
- •Female patients who are either pregnant or nursing
- •Women of child bearing potential who refuse or are not able to use a highly effective method of contraception as defined in the study protocol.
- •Sexually active males unless they use a condom during intercourse while taking drug and for 3 months after the last dose of study treatment.
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
EGF816
Experimental
Investigational treatment arm of EGF816 (nazartinib).
干预措施: EFG816 (Drug)
Investigator's Choice
Active Comparator
Investigator's Choice (erlotinib or gefitinib).
干预措施: erlotinib or gefitinib (Drug)
结局指标
主要结局
Progression Free Survival (PFS) by Blinded independent review committee (BIRC)
时间窗: Approximately 3 years
PFS using central BIRC assessment according to RECIST 1.1, is defined as the time from the date of randomization to the date of the first documented progression (as assessed by BIRC per RECIST 1.1) or death due to any cause, whichever occurs first.
次要结局
- Time to progression in Central Nervous System (CNS) per central neuro-radiologist BIRC(Approximately 3 years)
- Disease control rate (DCR) by central BIRC(Approximately 3 years)
- CNS DoR per central neuro-radiologist BIRC(Approximately 3 years)
- Charactise Plasma PK (Cmax) of EGF816(Day 1 of Cycles 1 to 6 inclusive (21 day cycle))
- Charactise Plasma PK (AUC) of EGF816(Day 1 of Cycles 1 to 6 inclusive (21 day cycle))
- Charactise Plasma PK (t1/2) of EGF816(Day 1 of Cycles 1 to 6 inclusive (21 day cycle))
- Patient Reported Outcome: Health Related Quality of Life (HRQoL) as measured by QLQ-C30 Questionnaire(Approximately 4 years)
- PFS after next-line of treatment (PFS2) using investigator assessment according to RECIST 1.1(Approximately 4 years)
- Overall response rate (ORR) by central BIRC(Approximately 3 years)
- Duration of response (DOR) by central BIRC(Approximately 3 years)
- Time to response (TTR) by central BIRC(Approximately 3 years)
- CNS ORR per central neuro-radiologist BIRC(Approximately 3 years)
- Overall Survival(Approximately 6 years)
- Patient Reported Outcome: Health Related Quality of Life (HRQoL) as measured by QLQ-LC13 Questionnaire(Approximately 4 years)
- Patient Reported Outcome: Health Related Quality of Life (HRQoL) as measured by EuroQoL-5 Dimension-5 (EQ-5D-5L) Questionnaire(Approximately 4 years)
- PFS by investigator(Approximately 3 years)
研究者
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