ChiCTR2500114640 版本V1.0 版本创建时间2025/12/16 08:51:11 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

ChiCTR2500114640 

最近更新日期：

Date of Last Refreshed on：

2025-12-16 08:51:03 

注册时间：

Date of Registration：

2025-12-16 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

奥氮平联合奥希替尼治疗 EGFR 21 外显子 L858R 突变局部晚期或转移性非小细胞肺癌的有效性和安全性：一项单臂、 前瞻性、多中心临床研究

Public title：

The efficacy and safety of olanzapine combined with osimertinib in the treatment of locally advanced or metastatic non-small cell lung cancer with EGFR exon 21 L858R mutation: A single-arm, prospective, multicenter clinical study

注册题目简写：

English Acronym：

研究课题的正式科学名称：

奥氮平联合奥希替尼治疗 EGFR 21 外显子 L858R 突变局部晚期或转移性非小细胞肺癌的有效性和安全性：一项单臂、 前瞻性、多中心临床研究

Scientific title：

The efficacy and safety of olanzapine combined with osimertinib in the treatment of locally advanced or metastatic non-small cell lung cancer with EGFR exon 21 L858R mutation: A single-arm, prospective, multicenter clinical study

研究课题代号(代码)：

Study subject ID：

在二级注册机构或其它机构的注册号：

The registration number of the Partner Registry or other register：

申请注册联系人：

柳芳 

研究负责人：

刘丽宏 

Applicant：

Fang Liu 

Study leader：

Lihong Liu 

申请注册联系人电话：

Applicant telephone：

+86 10 8420 5561

研究负责人电话：

Study leader's telephone：

+86 10 8523 1788

申请注册联系人传真 ：

Applicant Fax：

研究负责人传真：

Study leader's fax：

申请注册联系人电子邮件：

Applicant E-mail：

tcm_pharmacy@126.com

研究负责人电子邮件：

Study leader's E-mail：

hongllh@126.com

申请单位网址(自愿提供)：

Applicant website(voluntary supply)：

研究负责人网址(自愿提供)：

Study leader's website(voluntary supply)：

申请注册联系人通讯地址：

北京市朝阳区樱花东街2号中日友好医院药学部

研究负责人通讯地址：

朝阳区樱花东街2号

Applicant address：

Department of Pharmacy, China-Japan Friendship Hospital, No. 2, East Sakura Street, Chaoyang Distric

Study leader's address：

No.2 , Yinghua East Street, Chaoyang Dist. Beijing ,China

申请注册联系人邮政编码：

Applicant postcode：

研究负责人邮政编码：

Study leader's postcode：

申请人所在单位：

中日友好医院

Applicant's institution：

China-Japan Friendship Hospital

研究负责人所在单位：

中日友好医院

Affiliation of the Leader：

China-Japan Friendship Hospital

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

2025-KY-320-1

伦理委员会批件附件：

Approved file of Ethical Committee：

 查看附件View

批准本研究的伦理委员会名称：

中日友好医院临床研究伦理委员会

Name of the ethic committee：

Clinical Research Ethics Committee of China-Japan Friendship Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

2025-10-31 00:00:00

伦理委员会联系人：

闫旭

Contact Name of the ethic committee：

Yan Xu

伦理委员会联系地址：

朝阳区樱花东街2号

Contact Address of the ethic committee：

No.2 , Yinghua East Street, Chaoyang Dist. Beijing ,China

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 10 84206250

伦理委员会联系人邮箱：

Contact email of the ethic committee：

zryyec@126.com

研究实施负责（组长）单位：

中日友好医院

Primary sponsor：

China-Japan Friendship Hospital

研究实施负责（组长）单位地址：

朝阳区樱花东街2号

Primary sponsor's address：

No.2 , Yinghua East Street, Chaoyang Dist. Beijing ,China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

北京市

市(区县)：

Country：

China

Province：

Beijing

City：

单位(医院)：

中日友好医院

具体地址：

朝阳区樱花东街2号

Institution
hospital：

China-Japan Friendship Hospital

Address：

No.2 , Yinghua East Street, Chaoyang Dist. Beijing ,China

经费或物资来源：

齐鲁制药有限公司

Source(s) of funding：

Projects entrusted by enterprises and institutions（QILU PHARMACEUTICAL CO.,LTD）

Target disease：

EGFR exon 21 L858R mutation in locally advanced or metastatic non-small cell lung cancer

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 上市后药物 

Study phase：

4

研究设计：

单臂 

Study design：

Single arm 

研究目的：

主要目标：明确奥氮平联合奥希替尼治疗 EGFR 21 外显子 L858R 突变局部晚期或转移性NSCLC患者的有效性和安全性。 次要目标：探索该联合治疗方案对患者生活质量的影响，奥氮平对奥希替尼药代动力学参数的影响，以及奥希替尼及其代谢物血药浓度与临床疗效和安全性的相关性。  

Objectives of Study：

Primary objective: To determine the efficacy and safety of olanzapine combined with osimertinib in the treatment of locally advanced or metastatic NSCLC patients with EGFR 21 exon L858R mutation.Secondary objectives: To explore the effect of this combination regimen on the quality of life of patients, the effect of olanzapine on the pharmacokinetic parameters of osimertinib, and the correlation between the plasma concentrations of osimertinib and its metabolites and the clinical efficacy and safety.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

1.年龄 >= 18 周岁的男性或女性患者； 2.病理证实为非鳞状NSCLC，且明确诊断为腺癌； 3.新诊断的局部晚期(临床阶段IIIB, IIIC)或转移性NSCLC(临床阶段IVA或IVB)或复发性NSCLC(国际肺癌研究协会第9版[IASLC]胸肿瘤分期手册)，不适合手术或放疗； 4.组织或液体分子病理检测证实有EGFR突变21外显子L858R点突变，可以接受外院病理检查结果，提供检测报告； 5.WHO PS评分：0-1，并且在筛选时的前2周没有临床显著恶化； 6.预期生存期>=3个月； 7.至少存在1处按照RECIST 1.1版本标准可测量的靶病灶； 8.至少存在1个以前没有被照射过的可测量病灶，可以用CT或MRI在基线处精确测量，最长直径>=10 mm (淋巴结直径>=15 mm)，并且可以准确的重复测量。如果只有1个可测量的病灶存在，要求该病灶以前没有被照射，并且在基线肿瘤评估时的前14天内没有进行活检； 9.依从性好，受试者自愿加入本研究，并签署知情同意书，包括遵守知情同意书列出的要求和限制； 10.有生育潜力的女性或男性患者，必须从筛查开始使用可接受的避孕方法，直到停止研究治疗后至少6周；

Inclusion criteria

1. Male or female patients aged >= 18 years; 2. Pathologically confirmed non-squamous NSCLC with a definite diagnosis of adenocarcinoma; 3. Newly diagnosed locally advanced (clinical stage IIIB, IIIC) or metastatic NSCLC (clinical stage IVA or IVB) or recurrent NSCLC (International Association for the Study of Lung Cancer 9th edition [IASLC] Thoracic Tumour Staging Manual) not suitable for surgery or radiotherapy; 4. Tissue or liquid molecular pathology test confirming the presence of EGFR mutation exon 21 L858R point mutation, which can be accepted as a result of pathological examination in an outside hospital, providing the test report; 5. WHO PS score: 0-1 and no clinically significant deterioration in the first 2 weeks at screening; 6. expected survival >= 3 months; 7. presence of at least 1 target lesion measurable according to RECIST version 1.1 criteria; 8. Presence of at least 1 measurable lesion that has not been previously irradiated, that can be accurately measured at baseline by CT or MRI up to a maximum diameter of >= 10 mm (lymph node diameter of >= 15 mm), and that can be accurately and reproducibly measured. If only 1 measurable lesion is present, it is required that the lesion has not been previously irradiated and that no biopsy has been performed within the previous 14 days at the time of baseline tumour assessment; 9. compliance, subjects voluntarily enrolled in this study and signed an informed consent form, including adherence to the requirements and limitations outlined in the informed consent form; 10. female or male patients of childbearing potential must use an acceptable method of contraception from screening until at least 6 weeks after discontinuation of study treatment;

排除标准：

1.脊髓压迫；有症状或不稳定的或2周内接受过类固醇治疗的脑转移患者； 2.既往有间质性肺炎的病史、包括药物诱导间质性肺炎、需要类固醇治疗的放射性肺炎，或任何临床活动性间质性肺炎的患者； 3.存在任何严重或不受控制的全身性疾病的患者，包括不受控制的高血压、活动性出血、乙型肝炎、丙型肝炎和人类免疫缺陷病毒(HIV)在内的感染者； 4.存在以下心脏相关指标异常患者，包括3次心电图(ECGs)显示平均静息校正QT间期(QTc) >470毫秒；心电图显示节律、传导或形态异常者，如完全左束支传导阻滞、二级或三级心梗； 5.存在任何增加QTc延长风险的因素或心律失常事件风险的患者，如存在钾、镁、钙电解质异常、心力衰竭、先天性长QT综合征、长QT综合征家族史或已知延长QT间期的任何伴随药物； 6.骨髓储备或器官功能不足者，包括中性粒细胞、血小板、血红蛋白低于正常者；无肝转移患者ALT、AST>2.5倍正常值或肝转移患者>5倍正常值者；无肝转移患者总胆红素>2.5倍正常值或肝转移患者>3倍正常值者；CrCL<60mL/min者； 7.已证实为复合型NSCLC患者，病理提示合并其他类型成分，如鳞癌、肉瘤样、小细胞等； 8.合并其他部位原发肿瘤者； 9.在开始研究治疗时，存在未解决的先前全身治疗(如辅助化疗)导致大于CTCAE 1的不良反应，除脱发和2级铂相关神经病变外; 10.存在难治性恶心和呕吐、慢性胃肠道疾病、无法吞咽药品或既往行肠道切除可能影响药物充分吸收的患者; 11.前期已行针对局部晚期或晚期的任何系统性治疗者，包括化疗、靶向治疗、免疫治疗或任何生物治疗； 12.行辅助或者新辅助治疗结束时间不足3个月者。前期新辅助或辅助治疗有用过任何TKI治疗者； 13.4 周内做过手术或者放疗的患者，除外放置血管通路、通过纵隔镜检查活检或通过视频辅助胸腔镜手术 (VATS) 活检。既往放疗覆盖了30%骨髓者； 14.在接受治疗药物的前3周内仍有使用被认为是细胞色素P450 (CYP) 3A4的强诱导剂或抑制剂药物或草药补充剂； 15.在接受治疗药物的前4周内正在参加另一项临床研究者。随访期患者允许纳入； 16.如果患者不太可能遵守研究程序、限制和要求，则患者不应参与研究； 17.妊娠和哺乳期妇女； 18.对奥氮平或奥希替尼及其辅料过敏者；

Exclusion criteria：

1. Spinal cord compression; patients with symptomatic or unstable brain metastases, or those who have received steroid treatment within the past two weeks; 2. Patients with a history of interstitial pneumonia, including drug-induced interstitial pneumonia, radiation pneumonitis requiring steroid treatment, or any clinically active interstitial pneumonia; 3. Patients with any severe or uncontrolled systemic disease, including uncontrolled hypertension, active bleeding, hepatitis B, hepatitis C, and infection with human immunodeficiency virus (HIV); 4. Patients with abnormal cardiac parameters, including three electrocardiograms (ECGs) demonstrating a mean resting corrected QT interval (QTc) >470 milliseconds; ECGs showing rhythm, conduction, or morphological abnormalities such as complete left bundle branch block, second-degree or third-degree heart block; 5. Patients with any factors increasing the risk of QTc prolongation or arrhythmic events, such as electrolyte abnormalities (potassium, magnesium, calcium), heart failure, congenital long QT syndrome, family history of long QT syndrome, or known concomitant medications prolonging the QT interval; 6. Patients with inadequate bone marrow reserve or organ function, including those with neutropenia, thrombocytopenia, or haemoglobin below normal levels; patients without liver metastases with ALT or AST > 2.5 times the upper limit of normal (ULN), or those with liver metastases with >5 times ULN; patients without liver metastases with total bilirubin > 2.5 times ULN, or those with liver metastases with >3 times ULN; patients with creatinine clearance (CrCL) < 60 mL/min; 7. Patients with confirmed mixed-type NSCLC, where pathology indicates co-occurrence of other histological components such as squamous cell carcinoma, sarcomatoid, or small cell components; 8. Patients with concurrent primary tumours at other sites; 9. Presence of unresolved adverse reactions greater than Grade 1 per CTCAE from prior systemic therapy (e.g., adjuvant chemotherapy) at study treatment initiation, excluding alopecia and Grade 2 platinum-related neuropathy; 10. Patients with refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow medication, or prior intestinal resection potentially affecting drug absorption; 11. Patients who have previously received any systemic therapy for locally advanced or advanced disease, including chemotherapy, targeted therapy, immunotherapy, or any biological therapy; 12. Completion of adjuvant or neoadjuvant therapy within the preceding 3 months. Prior neoadjuvant or adjuvant therapy involving any TKI treatment; 13. Patients who underwent surgery or radiotherapy within the preceding 4 weeks, excluding placement of vascular access, mediastinoscopic biopsy, or video-assisted thoracoscopic surgery (VATS) biopsy. Prior radiotherapy covering ≥30% of the bone marrow; 14. Use of any drug or herbal supplement considered a strong inducer or inhibitor of cytochrome P450 (CYP) 3A4 within 3 weeks prior to receiving the study drug; 15. Participation in another clinical trial within 4 weeks prior to receiving the study drug. Patients may be included during follow-up periods; 16. Patients unlikely to comply with study procedures, restrictions, and requirements should not participate; 17. Pregnant or lactating women; 18. Individuals with known hypersensitivity to olanzapine, osimertinib, or any of their excipients;

研究实施时间：

Study execute time：

从 From 2026-01-01 00:00:00至 To 2028-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2026-01-01 00:00:00 至 To 2028-12-31 00:00:00  

干预措施：

Interventions：

组别：

试验组

样本量：

70

Group：

experimental group

Sample size：

干预措施：

奥希替尼联合奥氮平治疗

干预措施代码：

Intervention：

Osimertinib combined with olanzapine for treatment

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 北京市 

市(区县)：

  

Country：

China 

Province：

Beijing 

City：

 

单位(医院)：

中日友好医院 

单位级别：

三级甲等 

Institution
hospital：

China-Japan Friendship Hospital

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 北京市 

市(区县)：

  

Country：

China 

Province：

Beijing 

City：

 

单位(医院)：

中国医学科学院肿瘤医院 

单位级别：

三级甲等 

Institution
hospital：

Cancer Hospital Chinese Academy of Medical Sciences

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 北京市 

市(区县)：

  

Country：

China 

Province：

Beijing 

City：

 

单位(医院)：

中国医学科学院北京协和医院 

单位级别：

三级甲等 

Institution
hospital：

Peking Union Medical College Hospital

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 北京市 

市(区县)：

  

Country：

China 

Province：

Beijing 

City：

 

单位(医院)：

北京肿瘤医院（北京大学肿瘤医院） 

单位级别：

三级甲等 

Institution
hospital：

Beijing Cancer Hospital

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 北京市 

市(区县)：

  

Country：

China 

Province：

Beijing 

City：

 

单位(医院)：

首都医科大学附属北京胸科医院 

单位级别：

三级甲等 

Institution
hospital：

Beijing Chest Hospital, Capital Medical University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

不良事件及发生率

指标类型：

次要指标

Outcome：

Incidence of adverse events

Type：

Secondary indicator

测量时间点：

首次用药至疾病进展或由于不良反应中止治疗后28天

测量方法：

观察患者在治疗期间发生的不良事件（AE）及严重不良事件（SAE）（依据NCI-CTC V 5.0 标准），包括临床症状、生命体征及实验室检查中出现的异常，记录其严重程度、发生时间、持续时间、处理方法及预后，并判定其与奥氮平的相关性。

Measure time point of outcome：

The first dose was administered until 28 days after discontinuation of treatment due to adverse even

Measure method：

Observe the adverse events (AE) and serious adverse events (SAE) that occurred in patients during the treatment period (in accordance with the NCI-CTC V 5.0 standard), including clinical symptoms, vital signs and abnormalities in laboratory tests. Record their severity, occurrence time, duration, treatment methods and prognosis, and determine their correlation with olanzapine.

指标中文名：

1年无进展率

指标类型：

次要指标

Outcome：

The one-year no-progress rate

Type：

Secondary indicator

测量时间点：

在用药第9周（+/-3天）、第17周（+/-1周）进行评估，然后每12周评估一次胸、腹CT，直到RECIST 1.1定义了放射学疾病进展（脑核磁和骨扫描需根据研究者判断参与者病情需要进行检测）及生存期随访收集数据。

测量方法：

在用药第9周（+/-3天）、第17周（+/-1周）进行评估，然后每12周评估一次胸、腹CT，直到RECIST 1.1定义了放射学疾病进展（脑核磁和骨扫描需根据研究者判断参与者病情需要进行检测）及生存期随访收集数据。

Measure time point of outcome：

Assessments were conducted at Week 9 (+/-3 days) and Week 17 (+/-1 week) of treatment, followed by chest and abdominal CT scans every 12 weeks until radiological disease progression was defined according to RECIST 1.1 criteria (brain MRI and bone scans to be performed at the investigator's discretion based on participant condition). Survival follow-up data were collected concurrently.

Measure method：

Assessments were conducted at Week 9 (+/-3 days) and Week 17 (+/-1 week) of treatment, followed by chest and abdominal CT scans every 12 weeks until radiological disease progression was defined according to RECIST 1.1 criteria (brain MRI and bone scans to be performed at the investigator's discretion based on participant condition). Survival follow-up data were collected concurrently.

指标中文名：

脑转移控制率

指标类型：

次要指标

Outcome：

Control rate of brain metastases

Type：

Secondary indicator

测量时间点：

每12周

测量方法：

每12周评估一次胸、腹CT，直到RECIST 1.1定义了放射学疾病进展（脑核磁和骨扫描需根据研究者判断参与者病情需要进行检测）及生存期随访收集数据。

Measure time point of outcome：

Every 12 weeks

Measure method：

Chest and abdominal CT scans were evaluated every 12 weeks until RECIST 1.1 defined radiological disease progression (brain MRI and bone scans needed to be tested based on the investigator's judgment of the participants' conditions) and survival follow-up data were collected.

指标中文名：

肿瘤患者的疾病相关症状和健康相关生活质量

指标类型：

次要指标

Outcome：

Disease-related symptoms and health-related quality of life of cancer patients

Type：

Secondary indicator

测量时间点：

每12周

测量方法：

填写 EORTC QLQ-C30、EORTC QLQ-LC13量表

Measure time point of outcome：

Every 12 weeks

Measure method：

Fill in the EORTC QLQ-C30 and EORTC QLQ-LC13 scales

指标中文名：

疾病控制率

指标类型：

次要指标

Outcome：

Disease control rate

Type：

Secondary indicator

测量时间点：

每12周

测量方法：

每12周评估一次胸、腹CT，直到RECIST 1.1定义了放射学疾病进展（脑核磁和骨扫描需根据研究者判断参与者病情需要进行检测）及生存期随访收集数据。

Measure time point of outcome：

Every 12 weeks

Measure method：

Chest and abdominal CT scans were evaluated every 12 weeks until RECIST 1.1 defined radiological disease progression (brain MRI and bone scans needed to be tested based on the investigator's judgment of the participants' conditions) and survival follow-up data were collected.

指标中文名：

无进展生存期

指标类型：

主要指标

Outcome：

progression free surviva

Type：

Primary indicator

测量时间点：

至第一次出现疾病进展或任何原因导致死亡的日期

测量方法：

每12周评估一次胸、腹CT，直到RECIST 1.1定义了放射学疾病进展（脑核磁和骨扫描需根据研究者判断参与者病情需要进行检测）及生存期随访收集数据。

Measure time point of outcome：

The date of the first occurrence of disease progression or death from any cause

Measure method：

Chest and abdominal CT scans were evaluated every 12 weeks until RECIST 1.1 defined radiological disease progression (brain MRI and bone scans needed to be tested based on the investigator's judgment of the participants' conditions) and survival follow-up data were collected.

指标中文名：

缓解持续时间

指标类型：

次要指标

Outcome：

Duration of relief

Type：

Secondary indicator

测量时间点：

每12周

测量方法：

每12周评估一次胸、腹CT，直到RECIST 1.1定义了放射学疾病进展（脑核磁和骨扫描需根据研究者判断参与者病情需要进行检测）及生存期随访收集数据。

Measure time point of outcome：

Every 12 weeks

Measure method：

Chest and abdominal CT scans were evaluated every 12 weeks until RECIST 1.1 defined radiological disease progression (brain MRI and bone scans needed to be tested based on the investigator's judgment of the participants' conditions) and survival follow-up data were collected.

指标中文名：

焦虑/抑郁自评量表

指标类型：

次要指标

Outcome：

Self-rating Anxiety/Depression Scale

Type：

Secondary indicator

测量时间点：

每12周

测量方法：

填写焦虑/抑郁自评量表（SAS/SDS）

Measure time point of outcome：

Every 12 weeks

Measure method：

Fill out the Self-Rating Anxiety/Depression Scale (SAS/SDS)

指标中文名：

总客观缓解率

指标类型：

次要指标

Outcome：

Overall objective response rate

Type：

Secondary indicator

测量时间点：

每12周

测量方法：

每12周评估一次胸、腹CT，直到RECIST 1.1定义了放射学疾病进展（脑核磁和骨扫描需根据研究者判断参与者病情需要进行检测）及生存期随访收集数据。

Measure time point of outcome：

Every 12 weeks

Measure method：

Chest and abdominal CT scans were evaluated every 12 weeks until RECIST 1.1 defined radiological disease progression (brain MRI and bone scans needed to be tested based on the investigator's judgment of the participants' conditions) and survival follow-up data were collected.

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

血液

组织：

Sample Name：

Blood

Tissue：

人体标本去向

 使用后保存  

说明

Fate of sample：

Preservation after use  

Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

无

Randomization Procedure (please state who generates the random number sequence and by what method)：

NA

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法：

无

Blinding：

None

是否共享原始数据：

IPD sharing

No

共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：

无

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

None

数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：

病历报告表（CRF）及电子采集和管理系统（EDC）

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

Medical Record Report Form (CRF) and Electronic Capture and Management System (EDC)

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2025-12-16 08:51:03