ChiCTR2400080629 版本V1.0 版本创建时间2024/02/02 18:04:19 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：

ChiCTR2400080629 

最近更新日期：

Date of Last Refreshed on：

2024-02-02 18:04:12 

注册时间：

Date of Registration：

2024-02-02 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

一项评估舒沃替尼联合化疗治疗EGFR-TKIs耐药的EGFR敏感突变局部晚期或转移性非小细胞肺癌（NSCLC）的疗效与安全性的I/II期、单臂临床研究方案

Public title：

Sunvozertinib combined with chemotherapy for EGFRm + Locally Advanced or Metastasis NSCLC Patients After EGFR-TKI Treatment Failure:Phase I/II (WU-KONG36)

注册题目简写：

English Acronym：

研究课题的正式科学名称：

一项评估舒沃替尼联合化疗治疗EGFR-TKIs耐药的EGFR敏感突变局部晚期或转移性非小细胞肺癌（NSCLC）的疗效与安全性的I/II期、单臂临床研究方案

Scientific title：

Sunvozertinib combined with chemotherapy for EGFRm + Locally Advanced or Metastasis NSCLC Patients After EGFR-TKI Treatment Failure:Phase I/II (WU-KONG36)

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：

李丽 

研究负责人：

卢铀 

Applicant：

Li Li 

Study leader：

Lu You 

申请注册联系人电话：

Applicant telephone：

+86 138 8034 3287

研究负责人电话：

Study leader's telephone：

+86 189 8060 1763

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：

tracy.li_2010@hotmail.com

研究负责人电子邮件：

Study leader's E-mail：

radyoulu@hotmali.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：

四川省成都市武侯区国学巷37号

研究负责人通讯地址：

四川省成都市武侯区国学巷37号

Applicant address：

37 Guoxue Lane, Wuhou District, Chengdu, Sichuan

Study leader's address：

37 Guoxue Lane, Wuhou District, Chengdu, Sichuan

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：

四川大学华西医院

Applicant's institution：

West China Hospital,Sichuan University

研究负责人所在单位：

四川大学华西医院

Affiliation of the Leader：

West China Hospital,Sichuan University

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：

2023年审(2174)号

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：

四川大学华西医院生物医学伦理委员会

Name of the ethic committee：

Bioethics Committee of West China Hospital,Sichuan University

伦理委员会批准日期：

Date of approved by ethic committee：

2023-12-01 00:00:00

伦理委员会联系人：

邓绍林

Contact Name of the ethic committee：

Deng Shaolin

伦理委员会联系地址：

四川省成都市武侯区国学巷37号老八教412-413室

Contact Address of the ethic committee：

Room 412-413, Building 8 (Lao Ba Jiao), 37 Guoxue Lane, Wuhou District, Chengdu, Sichuan Province, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 28 8542 3237

伦理委员会联系人邮箱：

Contact email of the ethic committee：

研究实施负责（组长）单位：

四川大学华西医院

Primary sponsor：

West China Hospital,Sichuan University

研究实施负责（组长）单位地址：

四川省成都市武侯区国学巷37号

Primary sponsor's address：

37 Guoxue Lane, Wuhou District, Chengdu, Sichuan

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

四川

市(区县)：

Country：

China

Province：

Sichuan

City：

单位(医院)：

四川大学华西医院

具体地址：

四川省成都市武侯区国学巷37号

Institution
hospital：

West China Hospital,Sichuan University

Address：

37 Guoxue Lane, Wuhou District, Chengdu, Sichuan

经费或物资来源：

迪哲（江苏）医药股份有限公司

Source(s) of funding：

Dizal (Jiangsu) Pharmaceutical

Target disease：

cancer

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 I期+II期 

Study phase：

1-2

研究设计：

单臂 

Study design：

Single arm 

研究目的：

评估舒沃替尼联合化疗在EGFR-TKIs耐药的携带EGFR 突变的局部晚期或转移性非小细胞肺癌患者中的初步有效性。  

Objectives of Study：

to access the anti-tumor efficacy, safety and tolerability of Sunvozertinib combined with chemotherapy in patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) sensitizing mutations who have progressed following standard TKI therapy

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. 研究参研者须理解临床试验的要求和内容，并在临床试验、样本采集、分析前提供有手写签字和注明日期的知情同意书。 2. 18岁 ≤ 年龄 ≤ 80 岁。 3. 组织病理或细胞学确诊并记录局部进展（美国癌症联合委员会，AJCC第8版IIIB及IIIC期）或转移性（IV期）非鳞状细胞型非小细胞肺癌。 4. 由认可的当地实验室确认的EGFR敏感突变，包括19外显子缺失，21外显子L858R点突变，和20外显子T790M突变。 5. 签署知情同意书的过去两周内无疾病恶化且按美国东部肿瘤协作组（ECOG）标准评分为0 – 1，预测生存期 ≥ 12 周。 6. 研究参研者需经过EGFR-TKI靶向治疗后进展或对标准治疗不能耐受；如携带T790M突变需经过奥希替尼或其他第三代EGFR TKI治疗。 7. 既往未接受过针对局晚期或转移性疾病的系统性化疗。 8. 足够的骨髓造血或其他器官脏器储备 ? 血液学： ? 中性粒细胞绝对计数(ANC) ≥ 1.5 × 109/L ? 血小板 ≥ 100 × 109/L ? 血红蛋白 ≥ 9 g/dL ? 肝脏： ? 总胆红素 ≤ 1.5 × 正常值上限（ULN）；有Gilbert综合征（未结合的高胆红素血症）或肝转移的研究参研者，总胆红素 ≤ 3 × ULN ? 如无肝转移，谷丙转氨酶（ALT）≤ 2.5 × ULN及谷草转氨酶（AST）≤ 2.5 × ULN；或存在肝转移，ALT及AST ≤ 5 × ULN ? 肾脏：肌酐 ≤ 1.5 × ULN，同时通过Cockcroft-Gault法计算得到或测量得到的肌酐清除率 ≥ 60 mL/min ? 凝血： ? 国际标准化比率(INR) ≤ 1.5 × ULN ? 部分凝血活酶时间(APTT) ≤ 1.5 × ULN ? 其他： ? 血清淀粉酶 ≤ 1.5 × ULN， 且血清脂肪酶 ≤ 1.5 × ULN 9. 存在根据RECIST 1.1可测量的病灶：至少存在一个未经放射治疗的、长径 ≥10 mm （淋巴结病灶需短径 ≥15 mm）的病灶、并可在CT或MRI下对基线精准测量且可以重复测量的病灶。如研究参研者仅有经过放疗后的病灶，且该病灶已经明确为影像学进展并且可以测量，则可以选为靶病灶。 10. 有脑转移的研究参研者在满足以下条件可纳入至本研究：无症状或经局部治治疗（如WBRT或SRS）后症状稳定；不需要使用固醇类激素处理；距离完成局部治疗至少四周且不良反应恢复至基线。 11. 有女性伴侣并有生育意愿的男性研究参研者应在参与临床试验研究期间至最后一次给药后的6个月内使用屏障避孕法（如使用避孕套）。男性研究参研者在参与临床试验期间至最后一次给药后的6个月内不可捐精。如男性研究参研者有生育要求，建议在开始临床试验前冷冻精子。 12. 女性研究参研者应在筛选时至最后一次给药后的6周内应采取避孕措施、不能进行母乳喂养、筛选时妊娠测试（血或尿β-人绒毛膜促性腺激素）为阴性，或在筛选前符合以下标准： ? 绝经，定义为 ≥ 60岁，在停止外来激素治疗下停经至少12个月 ? 小于60岁的女性在以下条件下考虑为绝经：停经12个月，经检测促黄体生成素（LH）及促卵泡激素（FSH）水平符合停经状态 ? 持有相关不可逆的手术绝育治疗记录，如子宫切除、双侧卵巢切除术、或双侧输卵管切除术但未行输卵管连通术

Inclusion criteria

1. Research participants must understand the requirements and content of clinical trials, and provide a handwritten signed and dated informed consent form before clinical trials, sample collection, and analysis. 2. 18 years old ≤ age ≤ 80 years old. 3. Histopathology or cytology confirms and records local progression (American Joint Committee on Cancer, AJCC 8th edition stage IIIB and IIIC) or metastasis (stage IV) non-squamous non-small cell lung cancer. 4. EGFR sensitive mutations confirmed by accredited local laboratories, including exon 19 deletion, exon 21 L858R mutation, and exon 20 T790M mutation. 5. There is no disease progression within the past two weeks after signing the informed consent form and the score is 0 – 1 according to the Eastern Cooperative Oncology Group (ECOG) standard, and the predicted survival time is ≥ 12 weeks. 6. Study participants need to progress after EGFR-TKI targeted therapy or be intolerant to standard treatment; if they carry T790M mutation, they need to be treated with osimertinib or other third-generation EGFR TKI. 7. Have not received systemic chemotherapy for locally advanced or metastatic disease in the past. 8. Sufficient bone marrow hematopoiesis or other organ reserves ? Hematology: ? Absolute neutrophil count (ANC) ≥ 1.5 × 109/L ? Platelets ≥ 100 × 109/L ? Hemoglobin ≥ 9 g/dL ? Liver: ? Total bilirubin ≤ 1.5 × upper limit of normal (ULN); study participants with Gilbert syndrome (unconjugated hyperbilirubinemia) or liver metastases, total bilirubin ≤ 3 × ULN ? If there is no liver metastasis, alanine aminotransferase (ALT) ≤ 2.5 × ULN and aspartate aminotransferase (AST) ≤ 2.5 × ULN; or if liver metastasis is present, ALT and AST ≤ 5 × ULN ? Kidney: Creatinine ≤ 1.5 × ULN and creatinine clearance calculated or measured by the Cockcroft-Gault method ≥ 60 mL/min ? Coagulation: ? International Normalized Ratio (INR) ≤ 1.5 × ULN ? Partial thromboplastin time (APTT) ≤ 1.5 × ULN ? other: ? Serum amylase ≤ 1.5 × ULN, and serum lipase ≤ 1.5 × ULN 9. There is a measurable lesion according to RECIST 1.1: there is at least one lesion with a long diameter ≥10 mm (node ??lesions need a short diameter ≥15 mm) without radiotherapy, and the baseline can be accurately measured under CT or MRI and Lesions that can be measured repeatedly. If the study participant only has lesions after radiotherapy, and the lesions have been clearly shown to have radiographic progression and can be measured, they can be selected as target lesions. 10. Research participants with brain metastases can be included in this study if they meet the following conditions: asymptomatic or stable after local treatment (such as WBRT or SRS); no need for steroid treatment; long-term completion of local treatment At least four weeks before adverse effects return to baseline. 11. Male research participants who have a female partner and intend to have children should use barrier contraception (such as condoms) during their participation in the clinical trial study and within 6 months after the last dose. Male study participants cannot donate sperm while participating in the clinical trial and for 6 months after the last dose. If male research participants wish to have children, it is recommended that sperm be frozen before starting the clinical trial. 12. Female research participants should take contraceptive measures from the time of screening to 6 weeks after the last dose, cannot breastfeed, and have a negative pregnancy test (blood or urine beta-human chorionic gonadotropin) during screening. Or meet the following criteria before screening: ? Menopause, defined as ≥ 60 yearsold and the absence of menstruation for at least 12 months without exogenous hormone therapy ? Women younger than 60 years old are considered to be menopausal under the following conditions: 12 months of menopause, and tested levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) consistent with menopausal status ? Have records of irreversible surgical sterilization treatments, such as hysterectomy, bilateral oophorectomy, or bilateral salpingectomy without tubal connection.

排除标准：

1. 研究参研者接受过以下治疗须排除： ? 在研究药物首次给药前4周内，曾使用以EGFR为靶点的药物治疗。 ? 在研究药物首次给药前2周内，接受过任何细胞毒性化疗或其他抗肿瘤药物治疗。 ? 在首次给药前4周内接受放疗或尚未从放疗相关毒性中恢复至≤1级或基线水平。在首次给药14天之前， 可以接受立体定向放射外科手术和立体定向体部放射治疗（除外针对颅内病灶）。 ? 在舒沃替尼首次给药前1 – 2周内正在接受（或无法停止使用）可能的强效CYP3A抑制剂（1周）或诱导剂（2周）药物治疗或草本补充剂。 ? 首次给药前4周内接受过除诊断或活检外的其他重大手术，或预期在研究期间接受重大手术的研究参研者。 ? 其他正在研发阶段的药物须停止用药5个半衰期以上并与研究者协商后才可入组。 2. 存在脊髓压迫症或脑膜转移。 3. 2年内有恶性肿瘤病史（除外已经过充分治疗的皮肤基底细胞癌或原位子宫颈癌）。 4. 已知EGFR-TKI靶向治疗后存在明确的耐药机制，且有针对于此的可及治疗手段。 5. 在首次给药前，存在因前期治疗（例如辅助化疗、放疗等）引起的经CTCAE > 1级的不良事件（任何程度的脱发，2 级既往铂类治疗相关神经病变除外）。 6. 在首次给药前6个月内患有脑卒中或颅内出血病史。 7. 根据研究者的判断，存在任何严重或控制不佳的全身性疾病，包括控制不佳的高血压和活动性出血（如血友病、血管性血友病）。 8. 存在持续或活动性感染，包括但不局限于乙肝（HBV）、丙肝（HCV）、人类免疫缺陷病毒（HIV）及COVID-19感染（研究者判断有临床症状、体征等）的研究参研者。对于COVID-19检测将参考当地临床实践。 9. 以下任何心脏相关疾病或异常： 静息状态下心电图示校准后QTc间期（QTcF）> 470 msec 静息状态下心电图显示心率律、传导或图形的任何严重异常，如完全左束支阻滞、三级心脏阻滞、二级心脏阻滞、PR间期 > 250 msec 任何因素可引起QTcF延长或心率律失常疾病，如心衰、低钾血症、先天性QT延长综合征、有QT延长综合征家族史或其他40岁以下猝死疾病家族史或其他已知引起QT间期延长的疾病 患有心房颤动（药物引起且停药后已经恢复正常的除外）。 首次给药前 ≤ 6个月内心肌梗塞、New York Heart Association 2级充血性心力衰竭、药物控制不良的心律失常 10. 既往史有间质性肺病、药物引起的间质性肺病、需类固醇激素治疗的放射性肺炎或任何临床症状活跃的间质性肺病、免疫治疗引起的免疫性肺炎。 11. 难治性恶心及呕吐、慢性胃肠道疾病、吞咽药物困难或曾行肠切除术以致无法充分吸收舒沃替尼。 12. 首次用药前2周接种过活疫苗。 13. 正在哺乳或怀孕的女性。 14. 对舒沃替尼、化疗药物过敏。 15. 经研究者评估认为无法进行临床试验或可能缺乏临床试验的依从性的研究参研者不应参与本研究。

Exclusion criteria：

1. Research participants who have received the following treatments must be excluded: ? Have been treated with an EGFR-targeted drug within 4 weeks before the first dose of study drug. ? Received any cytotoxic chemotherapy or other anti-neoplastic drug treatment within 2 weeks before the first dose of study drug. ? Received radiation therapy within 4 weeks before the first dose or have not yet recovered from radiation therapy-related toxicity to ≤Grade 1 or baseline. Stereotactic radiosurgery and stereotactic body radiation therapy (except for intracranial lesions) can be received 14 days before the first dose. ? Are receiving (or unable to stop taking) medications or herbal supplements that may be strong CYP3A inhibitors (1 week) or inducers (2 weeks) within 1 – 2 weeks before the first dose of suvotinib. ? Study participants who have undergone major surgery other than diagnosis or biopsy within 4 weeks before the first dose, or who are expected to undergo major surgery during the study period. ? Other drugs under development must be discontinued for more than 5 half-lives and negotiated with the investigators before they can be included in the study. 2. There is spinal cord compression or meningeal metastasis. 3. Have a history of malignant tumors within 2 years (except for basal cell carcinoma of the skin or cervical cancer in situ that has been fully treated). 4. It is known that there is a clear resistance mechanism after EGFR-TKI targeted therapy, and there are accessible treatments for this. 5. Before the first dose, there are CTCAE > grade 1 adverse events (any degree of alopecia, except grade 2 neuropathy related to previous platinum therapy) caused by previous treatment (such as adjuvant chemotherapy, radiotherapy, etc.). 6. Have a history of stroke or intracranial hemorrhage within 6 months before the first dose. 7. According to the investigator's judgment, there is any serious or poorly controlled systemic disease, including poorly controlled hypertension and active bleeding (such as hemophilia, von Willebrand's disease). 8. Research participants with persistent or active infections, including but not limited to hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV) and COVID-19 infection (with clinical symptoms, signs, etc. as judged by the researcher) researcher. Local clinical practices will be referenced for COVID-19 testing. 9. Any of the following heart-related diseases or abnormalities: Resting ECG shows calibrated QTc interval (QTcF) > 470 msec Resting ECG showing any serious abnormality in heart rate rhythm, conduction or pattern, such as complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250 msec Any factor that can cause QTcF prolongation or arrhythmia, such as heart failure, hypokalemia, congenital QT prolongation syndrome, family history of QT prolongation syndrome or other sudden death diseases under 40 years of age, or other diseases known to cause QT Interval prolonging diseases Suffering from atrial fibrillation (unless it is caused by drugs and has returned to normal after stopping the drug). Myocardial infarction, New York Heart Association grade 2 congestive heart failure, and arrhythmias poorly controlled by drugs within ≤ 6 months before the first dose 10. Past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid treatment, or any interstitial lung disease with active clinical symptoms, or immune pneumonitis caused by immunotherapy. 11. Inability to fully absorb suvotinib due to refractory nausea and vomiting, chronic gastrointestinal diseases, difficulty swallowing drugs, or previous intestinal resection. 12. Get live vaccine 2 weeks before the first dose. 13. Women who are breastfeeding or pregnant. 14. Allergic to suvotinib and chemotherapy drugs. 15. Research participants who are assessed by the researcher as unable to conduct clinical trials or who may lack compliance with clinical trials should not participate in this study.

研究实施时间：

Study execute time：

从 From 2024-02-01 00:00:00至 To 2026-02-28 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2024-02-02 00:00:00 至 To 2025-02-28 00:00:00  

干预措施：

Interventions：

组别：

干预组

样本量：

40

Group：

Interventional group

Sample size：

干预措施：

舒沃替尼联合化疗（培美曲塞+铂类）

干预措施代码：

Intervention：

Sunvozertinib combined with chemotherapy(Pemetrexed +platinum)

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 四川 

市(区县)：

  

Country：

China 

Province：

Sichuan 

City：

 

单位(医院)：

四川大学华西医院 

单位级别：

三甲 

Institution
hospital：

West China Hospital,Sichuan University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

客观缓解率

指标类型：

主要指标

Outcome：

Objective Response Rate (ORR)

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

持续缓解时间

指标类型：

次要指标

Outcome：

Duration of Response (DoR)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

无进展生存期

指标类型：

次要指标

Outcome：

Progression-free survival (PFS)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

总生存期

指标类型：

次要指标

Outcome：

Overall survival (OS)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

不良事件数

指标类型：

次要指标

Outcome：

Number of participants with adverse events (AEs) according to CTCAE 5.0

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

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

 使用后销毁  

说明

Fate of sample：

Destruction 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 80 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）：

队列研究，无随机过程。

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

Cohort Study, no random processes.

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：

Blinding：

试验完成后的统计结果（上传文件）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

Yes

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）：

联系项目负责人

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

contact applicant

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：

病例记录表

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

Case Record Form

数据与安全监察委员会：

Data and Safety Monitoring Committee：

暂未确定/Not yet

注册人：

Name of Registration：

  2024-02-02 18:04:12