奥希替尼联合或不联合化疗与单独化疗作为 EGFRm 阳性可切除非小细胞肺癌患者新辅助治疗的研究 (NeoADAURA)
一项 III 期、随机、对照、多中心、3 组新辅助奥希替尼研究作为单一疗法或联合化疗与标准护理化疗单独治疗表皮生长因子受体突变阳性、可切除的非小细胞癌患者肺癌
研究概览
研究类型
注册 (实际的)
阶段
- 第三阶段
联系人和位置
学习地点
-
-
-
Beijing、中国、100142
- Research Site
-
Beijing、中国、100191
- Research Site
-
Beijing、中国、CN-100730
- Research Site
-
Changsha、中国、410013
- Research Site
-
Changsha、中国、410008
- Research Site
-
Chengdu、中国、610041
- Research Site
-
Chongqing、中国、400037
- Research Site
-
Guangzhou、中国、510120
- Research Site
-
Guangzhou、中国、510515
- Research Site
-
Guangzhou、中国、510062
- Research Site
-
Guangzhou、中国、510095
- Research Site
-
Hangzhou、中国、310022
- Research Site
-
Hangzhou、中国、310009
- Research Site
-
Kunming、中国、650118
- Research Site
-
Nanchang、中国、330006
- Research Site
-
Nantong、中国、226001
- Research Site
-
Shandong、中国
- Research Site
-
Shanghai、中国、200032
- Research Site
-
Shanghai、中国、200433
- Research Site
-
Shanghai、中国、200030
- Research Site
-
Suzhou、中国、215006
- Research Site
-
Wanzhou、中国、404000
- Research Site
-
Wenzhou、中国、CN-325000
- Research Site
-
Xiamen、中国、361004
- Research Site
-
Yangzhou、中国、225001
- Research Site
-
Ürümqi、中国、830000
- Research Site
-
-
-
-
-
Haifa、以色列、3109601
- Research Site
-
Jerusalem、以色列、91120
- Research Site
-
Kfar Saba、以色列、95847
- Research Site
-
Petah Tikva、以色列、49100
- Research Site
-
Ramat Gan、以色列、5265601
- Research Site
-
Tel Aviv、以色列、62748
- Research Site
-
-
-
-
-
Kazan'、俄罗斯、420029
- Research Site
-
Krasnoyarsk、俄罗斯、660133
- Research Site
-
Moscow、俄罗斯、105229
- Research Site
-
Nizhny Novgorod、俄罗斯、603081
- Research Site
-
Obninsk、俄罗斯、249036
- Research Site
-
Perm、俄罗斯、614990
- Research Site
-
Saint Petersburg、俄罗斯、197758
- Research Site
-
Saint Petersburg、俄罗斯、191036
- Research Site
-
-
-
-
-
Panagyurishte、保加利亚、4500
- Research Site
-
Pleven、保加利亚、5804
- Research Site
-
Sofia、保加利亚、1113
- Research Site
-
-
-
-
Ontario
-
Toronto、Ontario、加拿大、M5G 2N2
- Research Site
-
-
Quebec
-
Montreal、Quebec、加拿大、H4A 3J1
- Research Site
-
-
-
-
-
Mumbai、印度、400012
- Research Site
-
Namakkal、印度、637001
- Research Site
-
New Delhi、印度、110029
- Research Site
-
Varanasi、印度、221005
- Research Site
-
-
-
-
-
Taichung、台湾、40447
- Research Site
-
Taichung、台湾、40201
- Research Site
-
Tainan、台湾、73657
- Research Site
-
Taipei、台湾、235
- Research Site
-
Taipei、台湾、10002
- Research Site
-
Taipei、台湾、112
- Research Site
-
Taipei、台湾、110
- Research Site
-
-
-
-
-
Ankara、土耳其(türkiye)、6500
- Research Site
-
Ankara、土耳其(türkiye)、06800
- Research Site
-
Ankara、土耳其(türkiye)、06010
- Research Site
-
Istanbul、土耳其(türkiye)、34010
- Research Site
-
Istanbul、土耳其(türkiye)、34214
- Research Site
-
Malatya、土耳其(türkiye)、44280
- Research Site
-
-
-
-
-
Aguascalientes、墨西哥、20230
- Research Site
-
D.F、墨西哥、14050
- Research Site
-
Mexico City、墨西哥、'14080
- Research Site
-
-
-
-
-
Graz、奥地利、8036
- Research Site
-
Vienna、奥地利、1210
- Research Site
-
-
-
-
-
Barretos、巴西、14784-400
- Research Site
-
Fortaleza、巴西、60135-040
- Research Site
-
Jaú、巴西、17204310
- Research Site
-
Porto Alegre、巴西、90610-000
- Research Site
-
Porto Alegre、巴西、90035-000
- Research Site
-
Recife、巴西、52010-075
- Research Site
-
Rio de Janeiro、巴西、22271-110
- Research Site
-
Santa Maria、巴西、97015-450
- Research Site
-
São José do Rio Preto、巴西、15090-000
- Research Site
-
São Paulo、巴西、04038-034
- Research Site
-
São Paulo、巴西、04501-000
- Research Site
-
São Paulo、巴西、01327-001
- Research Site
-
-
-
-
-
Berlin、德国、12351
- Research Site
-
Bielefeld、德国、33611
- Research Site
-
Cologne、德国、51109
- Research Site
-
Esslingen a.N.、德国、73730
- Research Site
-
Freiburg im Breisgau、德国、79106
- Research Site
-
Gauting、德国、82131
- Research Site
-
Georgsmarienhütte、德国、49124
- Research Site
-
Halle、德国、06120
- Research Site
-
Oldenburg、德国、26121
- Research Site
-
Würzburg、德国、97067
- Research Site
-
-
-
-
-
Bari、意大利、70124
- Research Site
-
Florence、意大利、50134
- Research Site
-
Monza、意大利、20900
- Research Site
-
Orbassano、意大利、10043
- Research Site
-
Padova、意大利、35128
- Research Site
-
Rozzano、意大利、20089
- Research Site
-
Varese、意大利、21100
- Research Site
-
-
-
-
-
Akashi-shi、日本、673-8558
- Research Site
-
Bunkyō City、日本、113-8431
- Research Site
-
Chiba、日本、260-8677
- Research Site
-
Hiroshima、日本、734-8551
- Research Site
-
Kashiwa、日本、227-8577
- Research Site
-
Kyoto、日本、606-8507
- Research Site
-
Kōtoku、日本、135-8550
- Research Site
-
Niigata、日本、951-8566
- Research Site
-
Osaka、日本、541-8567
- Research Site
-
Sakai、日本、590-0197
- Research Site
-
Sakaishi、日本、591-8555
- Research Site
-
Sendai、日本、981-0914
- Research Site
-
Shinjuku-ku、日本、160-0023
- Research Site
-
Sunto-gun、日本、411-8777
- Research Site
-
Yokohama、日本、241-8515
- Research Site
-
-
-
-
-
Las Condes、智利、7560908
- Research Site
-
Santiago、智利、7500713
- Research Site
-
Santiago、智利、7500921
- Research Site
-
-
-
-
-
Avignon、法国、84902
- Research Site
-
Bordeaux、法国、33000
- Research Site
-
-
-
-
-
Olsztyn、波兰、10-357
- Research Site
-
-
-
-
-
Bangkok、泰国、10330
- Research Site
-
Bangkok、泰国、10400
- Research Site
-
Chiang Mai、泰国、50200
- Research Site
-
Khon Kaen、泰国、40002
- Research Site
-
Pathum Thani、泰国、12120
- Research Site
-
Phisanulok、泰国、65000
- Research Site
-
-
-
-
-
Winterthur、瑞士、8401
- Research Site
-
Zurich、瑞士、CH-8091
- Research Site
-
-
-
-
-
La Libertad、秘鲁、13013
- Research Site
-
Lima、秘鲁、LIMA 34
- Research Site
-
Lima、秘鲁、15036
- Research Site
-
Lima、秘鲁、L41
- Research Site
-
Lima、秘鲁、0051
- Research Site
-
-
-
-
California
-
Duarte、California、美国、91010
- Research Site
-
Irvine、California、美国、92618
- Research Site
-
San Francisco、California、美国、94143
- Research Site
-
Santa Monica、California、美国、90404
- Research Site
-
Santa Rosa、California、美国、95403
- Research Site
-
-
Massachusetts
-
Boston、Massachusetts、美国、02215
- Research Site
-
-
New Hampshire
-
Lebanon、New Hampshire、美国、03756
- Research Site
-
-
New York
-
Commack、New York、美国、11725
- Research Site
-
New York、New York、美国、10032
- Research Site
-
-
Texas
-
Houston、Texas、美国、77030
- Research Site
-
-
Virginia
-
Fairfax、Virginia、美国、22031
- Research Site
-
-
Washington
-
Seattle、Washington、美国、98104
- Research Site
-
-
-
-
-
Birmingham、英国、B9 5SS
- Research Site
-
Liverpool、英国、L7 8YA
- Research Site
-
-
-
-
-
Barcelona、西班牙、08035
- Research Site
-
Madrid、西班牙、28040
- Research Site
-
Majadahonda、西班牙、28222
- Research Site
-
Málaga、西班牙、29010
- Research Site
-
-
-
-
-
Hanoi、越南、100000
- Research Site
-
Ho Chi Minh City、越南、700000
- Research Site
-
Ho Chi Minh City、越南、70000
- Research Site
-
-
-
-
-
Daegu、韩国、41404
- Research Site
-
Hwasun-gun、韩国、58128
- Research Site
-
Incheon、韩国、21431
- Research Site
-
Seoul、韩国、08308
- Research Site
-
Seoul、韩国、02447
- Research Site
-
Seoul、韩国、42601
- Research Site
-
Yangsan、韩国、50612
- Research Site
-
-
参与标准
资格标准
适合学习的年龄
接受健康志愿者
描述
纳入标准:
- 男性或女性,至少 18 岁。 对于年龄 <20 岁且在日本入组的患者,应获得患者及其合法代表的书面知情同意书
- 组织学或细胞学证明具有完全可切除(II - IIIB N2 期)疾病的非鳞状 NSCLC(根据 IASLC 癌症分期手册第 8 版 [IASLC 胸部肿瘤分期手册 2016])。
- 原发性 NSCLC 的完全手术切除必须被认为是可以实现的,如通过 MDT 评估(应包括专门从事肿瘤手术的胸外科医生)所评估的那样。
- 东部合作肿瘤组 (ECOG) 入组时 PS 为 0 或 1,在基线前或首次给药前 2 周内没有恶化
- 包含已知与 EGFR-TKI 敏感性相关的 2 种常见 EGFR 突变之一的肿瘤(Ex19del、L858R),单独或与其他 EGFR 突变(即 T790M、G719X、Exon20 插入、S7681 和 L861Q)组合。
排除标准:
- ILD、药物引起的 ILD、需要类固醇治疗的放射性肺炎的既往病史,或任何临床活动性 ILD 的证据。
- 另一种原发性恶性肿瘤的病史,但以下情况除外: 在首次给予研究产品 (IP) 前 ≥ 2 年以治愈为目的进行治疗且无已知活动性疾病且复发风险低的恶性肿瘤;没有疾病证据的非黑色素瘤皮肤癌或恶性雀斑得到充分治疗;没有疾病证据的原位癌得到充分治疗
- 将术前放疗作为其护理计划一部分的患者
- 混合小细胞和 NSCLC 组织学
- I、IIIB N3、IIIC、IVA 和 IVB 期 NSCLC
- T4 肿瘤浸润主动脉、食道和/或心脏;和/或任何庞大的 N2 疾病
- 适合仅接受肺段切除术或楔形切除术的患者
- 之前接受过任何针对 NSCLC 的全身抗癌治疗,包括化疗、生物疗法、免疫疗法或任何研究药物
- 既往接受过 EGFR-TKI 治疗
- 目前正在使用(或在接受首次研究治疗之前无法停止使用)已知是细胞色素 P450 (CYP) 3A4 强诱导剂的药物或草药补充剂(至少 3 周前)
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
安慰剂比较:第 1 组:安慰剂联合铂类化疗
安慰剂加上研究者选择的基于铂的标准治疗化疗(培美曲塞/卡铂或培美曲塞/顺铂)
|
口服
顺铂 (75mg/m2) 在每 3 周周期的第 1 天与培美曲塞一起给药,共 3 个周期。
卡铂 (AUC5) 在每 3 周周期的第 1 天与培美曲塞一起给药,共 3 个周期
培美曲塞 (500 mg/m2) 在每 3 周周期的第 1 天与顺铂或卡铂联合给药,共 3 个周期
|
|
实验性的:第 2 组:奥希替尼联合铂类化疗
奥希替尼 80 mg QD(剂量可根据研究者的判断减少至 40 mg QD)加上研究者选择的铂类标准治疗化疗(培美曲塞/卡铂或培美曲塞/顺铂)
|
顺铂 (75mg/m2) 在每 3 周周期的第 1 天与培美曲塞一起给药,共 3 个周期。
卡铂 (AUC5) 在每 3 周周期的第 1 天与培美曲塞一起给药,共 3 个周期
培美曲塞 (500 mg/m2) 在每 3 周周期的第 1 天与顺铂或卡铂联合给药,共 3 个周期
口服
其他名称:
|
|
实验性的:第 3 组:奥希替尼单药治疗
奥希替尼 80 mg QD(剂量可根据研究者的判断减少至 40 mg QD)
|
口服
其他名称:
|
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Major Pathological Response (MPR) - IASLC Method
大体时间:From date of randomization to an average of 12 weeks after the first dose
|
Defined as ≤10% viable cancer cells in the surgical specimen, as assessed per central pathology laboratory post-surgery (IASLC method).
Patients will only be considered to have an MPR if they also have an R0 margin result.
|
From date of randomization to an average of 12 weeks after the first dose
|
|
Major Pathological Response (MPR) - Chemotherapy Method
大体时间:From date of randomization to an average of 12 weeks after the first dose
|
Defined as ≤10% viable cancer cells in the surgical specimen, as assessed per central pathology laboratory post-surgery (chemotherapy method).
Patients will only be considered to have an MPR if they also have an R0 margin result.
|
From date of randomization to an average of 12 weeks after the first dose
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Pathological Complete Response (pCR) - IASLC Method
大体时间:From date of randomization to an average of 12 weeks after the first dose
|
Defined as absence of any viable cancer cells in the dissected tumour samples, including the main tumour, lymph nodes, and margins as assessed per central pathology laboratory post-surgery using IASLC method.
Patients will only be considered to have pCR if they also have an R0 margin result based on site assessment.
|
From date of randomization to an average of 12 weeks after the first dose
|
|
Pathological Complete Response (pCR) - Chemotherapy Method
大体时间:From date of randomization to an average of 12 weeks after the first dose
|
Defined as absence of any viable cancer cells in the dissected tumour samples, including the main tumour, lymph nodes, and margins as assessed per central pathology laboratory post-surgery using chemotherapy method.
Patients will only be considered to have pCR if they also have an R0 margin result based on site assessment.
|
From date of randomization to an average of 12 weeks after the first dose
|
|
Downstaging
大体时间:From date of randomization to an average of 12 weeks after the first dose.
|
Measured using pathologic mediastinal lymph node evaluation.
Pathological downstaging is defined as baseline N2 patients becoming N1/N0 or N1 to N0 at the time of surgery.
Only patients with pathological staging at both baseline and surgery are included in this analysis.
|
From date of randomization to an average of 12 weeks after the first dose.
|
|
Concordance of EGFRm Status Between Tumor Tissue DNA and Patient-matched Plasma-derived ctDNA (Mutation Ex19Del or L858R)
大体时间:Screening/Baseline
|
Comparing the baseline central cobas® EGFR Mutation Test V2 between tumor tissue DNA and matched plasma ctDNA results (excluding invalid results).
Since this endpoint uses pre-randomization data, treatment arms were combined for the analysis.
|
Screening/Baseline
|
|
Concordance of EGFR Mutation Status Between the Local and Central Test Results From Baseline Tumor Samples (Mutation Ex19Del or L858R)
大体时间:Screening/Baseline
|
Comparing the local EGFR mutation test result used for patient selection with the retrospective baseline central cobas® EGFR Mutation Test V2 results (excluding invalid results).
Since this endpoint uses pre-randomization data, treatment arms were combined for the analysis.
|
Screening/Baseline
|
|
Change From Baseline in EORTC QLQ-C30 Primary Subscale Scores (Neoadjuvant Period)
大体时间:Assessed at baseline, Cycle 2 Day1, Cycle 3 Day1, and Pre-surgical assessment (on D64, -1 to +21 days ).
|
Average change from baseline across all visits are reported.
The analysis was performed using a MMRM analysis on the change from baseline in the score at each visit, including subject (random effect), treatment, visit (fixed effect & repeated measure) and treatment by visit interaction as explanatory variables, with the baseline score as a covariate along with the baseline score by assessment interaction.
EORTC QLQ-C30 has 30 questions and questions are combined to produce symptom scales, individual symptom items, functional scales, and global health status (GHS)/quality of life (QoL).
Each of the scale/items range from 0-100 after a linear transformation.
Positive change from baseline scores on the GHS/QoL and functioning scales indicate improvement on health status/function, and negative change scores on symptom scales/items represent less symptom severity/improvement on symptom status.
|
Assessed at baseline, Cycle 2 Day1, Cycle 3 Day1, and Pre-surgical assessment (on D64, -1 to +21 days ).
|
|
Change From Baseline in EORTC QLQ-LC13 Primary Subscale Scores (Neoadjuvant Period)
大体时间:Assessed at baseline, Cycle 2 Day1, Cycle 3 Day1, and Pre-surgical assessment (on D64, -1 to +21 days).
|
Average change from baseline across all visits are reported. The analysis was performed using a MMRM analysis on the change from baseline in the score at each visit, including subject (as a random effect), treatment, visit (as fixed effect and repeated measure) and treatment by visit interaction as explanatory variables, with the baseline score as a covariate along with the baseline score by assessment interaction. EORTC QLQ-LC13 has 13 questions and scores range from 0-100 after a linear transformation. Questions assess cough, hemoptysis, dyspnea, site specific pain, sore mouth, dysphagia, peripheral neuropathy, and alopecia and pain medication. While the QLQ-LC13 includes more scales, only the Coughing, Pain in chest, and Dyspnea subscale scores were analyzed for this endpoint. Negative change from baseline scores indicates less symptom severity, and thus improvement on health status. |
Assessed at baseline, Cycle 2 Day1, Cycle 3 Day1, and Pre-surgical assessment (on D64, -1 to +21 days).
|
|
PK Plasma Concentrations of Osimertinib
大体时间:From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days)
|
Summary of plasma concentrations (nM) of Osimertinib
|
From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days)
|
|
PK Plasma Concentrations of AZ5104
大体时间:From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days)
|
Summary of plasma concentrations (nM) of AZ5104
|
From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days)
|
其他结果措施
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
治愈率
大体时间:从手术到手术后5年
|
治愈率定义为本研究中在完成手术后的一段时间内仍然活着并且没有疾病的人的百分比。
此处将与 OS 分析同时计算 5 年里程碑治愈率。
|
从手术到手术后5年
|
|
通过 CTCAE 5.0 和其他临床变量评估的不良事件数量,用于新辅助奥希替尼作为单一疗法或术前化疗与单独化疗相比的安全性和耐受性概况
大体时间:对于未接受手术的患者,从入组时间到最后一次研究治疗的最后一剂后 28 天,或手术后 90 天
|
其他临床变量包括死亡、实验室数据、生命体征(脉搏和血压)、ECG、LVEF、ECOG 体能状态和眼科评估
|
对于未接受手术的患者,从入组时间到最后一次研究治疗的最后一剂后 28 天,或手术后 90 天
|
|
使用血浆来源的循环游离肿瘤 DNA (ctDNA) 进行 MPR
大体时间:从随机分组之日到第一次给药后平均 12 周
|
从随机分组之日到第一次给药后平均 12 周
|
合作者和调查者
赞助
调查人员
- 首席研究员:Jamie Chaft, MD、Memorial Sloan Kettering, USA
- 首席研究员:Walter Weder, MD、Thoraxchirurgie Bethanien, Switzerland
- 首席研究员:keiju Aokage, MD、National Cancer Center Hospital East, Japan
出版物和有用的链接
一般刊物
- Tsuboi M, Weder W, Escriu C, Blakely C, He J, Dacic S, Yatabe Y, Zeng L, Walding A, Chaft JE. Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for EGFR-mutated resectable non-small-cell lung cancer: NeoADAURA. Future Oncol. 2021 Nov;17(31):4045-4055. doi: 10.2217/fon-2021-0549. Epub 2021 Jul 19.
- Murat-Onana ML, Ramalingam SS, Janne PA, Gray JE, Ahn MJ, John T, Yatabe Y, Huang X, Rukazenkov Y, Javey M, Brown H, Li-Sucholeiki X. EGFR mutation testing across the osimertinib clinical program. Lung Cancer. 2025 Jun;204:108549. doi: 10.1016/j.lungcan.2025.108549. Epub 2025 Apr 18.
- He J, Tsuboi M, Weder W, Chen KN, Hochmair MJ, Shih JY, Lee SY, Lee KY, Nhung NV, Saeteng S, Liu L, Xing L, Gia NH, Murakami S, Han Y, Saavedra MP, Yoon SH, Teixeira CHA, Escriu C, Martinez-Marti A, Blakely CM, Yatabe Y, Dacic S, Rukazenkov Y, Huang X, Dayal A, Chaft JE; NeoADAURA Investigators. Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non-Small Cell Lung Cancer. J Clin Oncol. 2025 Sep 10;43(26):2875-2887. doi: 10.1200/JCO-25-00883. Epub 2025 Jun 2.
- Lee JB, Choi SJ, Shim HS, Park BJ, Lee CY, Sudhaman S, Velichko S, Hong MH, Cho BC, Lim SM. Neoadjuvant and Adjuvant Osimertinib in Stage IA to IIIA, EGFR-Mutant NSCLC (NORA). J Thorac Oncol. 2025 May;20(5):641-650. doi: 10.1016/j.jtho.2024.12.023. Epub 2024 Dec 26.
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- D516AC00001
- 2020-000058-89 (EudraCT编号)
- 2022-502606-33-00 (注册表标识符:CTIS (EU))
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)?
IPD 计划说明
IPD 共享时间框架
IPD 共享访问标准
IPD 共享支持信息类型
- 研究方案
- 树液
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.