中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2500106355
最近更新日期： Date of Last Refreshed on：	2025-07-22 17:45:40
注册时间： Date of Registration：	2025-07-22 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	胸腔灌注依沃西单抗治疗肺癌恶性胸腔积液的一项前瞻性、单中心、II期性临床研究
Public title：	A Prospective, Single-Center, Phase II Clinical Study on Intrapleural Perfusion of Ivosidenib for Malignant Pleural Effusion in Lung Cancer
注册题目简写：
English Acronym：
研究课题的正式科学名称：	胸腔灌注依沃西单抗治疗肺癌恶性胸腔积液的一项前瞻性、单中心、II期性临床研究
Scientific title：	A Prospective, Single-Center, Phase II Clinical Study on Intrapleural Perfusion of Ivosidenib for Malignant Pleural Effusion in Lung Cancer
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：	王海永	研究负责人：	王海永
Applicant：	Wang Haiyong	Study leader：	Wang Haiyong
申请注册联系人电话： Applicant telephone：	+86 15665878316	研究负责人电话： Study leader's telephone：	+86 531 67626711
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：	wanghaiyong6688@126.com	研究负责人电子邮件： Study leader's E-mail：	wanghaiyong6688@163.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：	山东省济南市槐荫区济兖路440号	研究负责人通讯地址：	山东省济南市槐荫区济兖路440号
Applicant address：	No.440,Jiyan Road,HuaiyinDistrict,Jinan,Shandong Province	Study leader's address：	No. 440, Jiyan Road, Huaiyin District, Jinan City, Shandong Province
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：	山东第一医科大学附属肿瘤医院
Applicant's institution：	Cancer Hospital Affiliated to Shandong First Medical University
研究负责人所在单位：	山东第一医科大学附属肿瘤医院（山东省肿瘤防治研究院、山东省肿瘤医院）
Affiliation of the Leader：	Shandong First Medical University and Shandong Academy of Medical Sciences (Shandong Cancer Hospital ＆Institute)

是否获伦理委员会批准：	是
Approved by ethic committee：	Yes
伦理委员会批件文号： Approved No. of ethic committee：	SDZLEC2025-251-02	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：	山东第一医科大学附属肿瘤医院伦理委员会
Name of the ethic committee：	Ethics Committee of the Affiliated Cancer Hospital of Shandong First Medical University
伦理委员会批准日期： Date of approved by ethic committee：	2025-07-10 00:00:00
伦理委员会联系人：	李朝伟
Contact Name of the ethic committee：	Li ChaoWei
伦理委员会联系地址：	山东省济南市槐荫区济兖路440号
Contact Address of the ethic committee：	No. 440, Jiyan Road, Huaiyin District, Jinan City, Shandong Province
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 531 67626929	伦理委员会联系人邮箱： Contact email of the ethic committee：	sdzlllh803@126.com

研究实施负责（组长）单位：

山东第一医科大学附属肿瘤医院（山东省肿瘤防治研究院、山东省肿瘤医院）

Primary sponsor：

Shandong First Medical University and Shandong Academy of Medical Sciences (Shandong Cancer Hospital ＆Institute)

研究实施负责（组长）单位地址：

山东省济南市槐荫区济兖路440号

Primary sponsor's address：

No. 440, Jiyan Road, Huaiyin District, Jinan City, Shandong Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	山东省	市(区县)：
Country：	China	Province：	Shandong	City：
单位(医院)：	山东第一医科大学附属肿瘤医院（山东省肿瘤防治研究院、山东省肿瘤医院）	具体地址：	山东省济南市槐荫区济兖路440号
Institution hospital：	Shandong First Medical University and Shandong Academy of Medical Sciences (Shandong Cancer Hospital ＆Institute)	Address：	No. 440, Jiyan Road, Huaiyin District, Jinan City, Shandong Province

经费或物资来源：

科研基金

Source(s) of funding：

Scientific research donation

研究疾病：

肺癌恶性胸腔积液

Target disease：

Malignant Pleural Effusion in Lung Cancer

研究疾病代码：

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

II期临床试验

Study phase：

2

研究设计：

单臂

Study design：

Single arm

研究目的：

主要目的评估依沃西单抗治疗肺癌恶性胸腔积液（MPE）的客观缓解率（ORR），由研究者基于WHO疗效评价标准评估。次要目的评估评估依沃西单抗治疗肺癌恶性胸腔积液患者的至下一次穿刺和/或引流的时间（TTNP）；评估依沃西单抗治疗肺癌恶性胸腔积液的血管内皮生长因子(VEGF)水平；评估依沃西单抗治疗肺癌恶性胸腔积液的无进展生存期（PFS）；评估依沃西单抗治疗肺癌恶性胸腔积液的总生存期（OS）；由通过欧洲癌症研究和治疗组织的生活质量调查问卷核心30项评分（EORTC QLQ-C30）和肺癌症状量表（EORTC QLQ-LC13）评估依沃西单抗治疗NSCLC恶性胸腔积液的健康相关生活质量（HRQoL）；评估依沃西单抗治疗肺癌恶性胸腔积液的的安全性和耐受性；探索性目的收集患者灌注前后的胸腔积液样本、血液样本，探索依沃西单抗控制恶性胸腔积液的作用机制。

Objectives of Study：

Primary Objective To evaluate the objective response rate (ORR) of ivosidenib (Note: Confirm drug name) in the treatment of malignant pleural effusion (MPE) in lung cancer, as assessed by investigators based on the WHO response evaluation criteria. Secondary Objectives To assess the time to next pleural puncture and/or drainage (TTNP) in lung cancer patients with MPE treated with ivosidenib. To evaluate changes in vascular endothelial growth factor (VEGF) levels in pleural effusion after ivosidenib treatment. To determine the progression-free survival (PFS) of MPE patients receiving ivosidenib. To measure the overall survival (OS) of MPE patients treated with ivosidenib. To assess health-related quality of life (HRQoL) using the EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30) and the EORTC QLQ-LC13 (lung cancer-specific module) in NSCLC patients with MPE receiving ivosidenib. To evaluate the safety and tolerability of ivosidenib in the treatment of MPE. Exploratory Objectives To collect pleural effusion samples and blood samples before and after treatment to investigate the mechanism of action of ivosidenib in controlling MPE.

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

Inclusion criteria

1.Willing to sign the informed consent form.
2.Age >=18 and <=75 years at enrollment, both male and female.
3.Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2.
4.Life expectancy >=3 months.
5.Patients with pathologically or cytologically confirmed lung cancer.
6.Radiological evidence of moderate-to-large pleural effusion, with cytologically confirmed malignant pleural effusion (MPE) requiring drainage as assessed by the investigator.
7.Adequate organ and bone marrow function, defined as follows: a) Hematologic:  Absolute neutrophil count (ANC) >=1.5×10⁹/L  Platelets (PLT) >=100×10⁹/L  Hemoglobin (Hb) >=9 g/dL  b) Hepatic:  Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) <=2.5×upper limit of normal (ULN)  Total bilirubin (TBIL) <=1.5×ULN  c) Renal:  Creatinine clearance (CrCl) >=60 mL/min (calculated by Cockcroft-Gault formula; see Appendix)  d) Coagulation:  International normalized ratio (INR), activated partial thromboplastin time (aPTT), and prothrombin time (PT) <=1.5×ULN  e) Cardiac:  Left ventricular ejection fraction (LVEF) >=50% as measured by echocardiography (ECHO) or multigated acquisition (MUGA) scan;
8.For Female Patients of Childbearing Potential: Negative serum pregnancy test at screening.  Must agree to use highly effective non-hormonal contraception during treatment and for >=3 months after the last dose of the investigational drug.
9.Voluntarily participates in the study and provides written informed consent.  Demonstrates good compliance and is willing to adhere to follow-up procedures.

排除标准：

1.既往曾进行过胸腔内注射贝伐珠单抗或PD-1/PD-L1抑制剂； 2.在前 2 周内接受过抗肿瘤治疗，包括化疗、胸部放疗、靶向治疗、免疫治疗和生物治疗； 3.双侧胸腔积液或同时合并腹腔积液，或同时合并心包积液； 4.胸腔积液为包裹性积液或严重分隔；或合并乳糜胸；或合并感染性胸腔积液； 5.既往给予胸腔穿刺/引流后，仍有胸闷、气促，较前无明显缓解，经研究者判定仍有肺不张、肺实变或其他严重影响呼吸功能的肺部病变情况存在。 6.已知对本方案药物及其组分有过敏史，有免疫缺陷史，或有器官移植史； 7.首次给药前4周内发生严重感染，包括但不局限于伴有需要住院治疗的合并症、败血症或严重肺炎；在首次给药前2周内接受过全身抗感染治疗的活动性感染（不包括乙型肝炎或丙型肝炎的抗病毒治疗）； 8.有严重出血倾向或凝血功能障碍病史；首次给药前4周内存在具有显著临床意义的出血症状，包括但不限于消化道出血、咳血（定义为咳出或咯出≥1茶匙鲜血或小血块或只咳血无痰液，允许痰中带血者入组）、鼻腔出血（不包括鼻衄出血及回缩性涕血）；首次用药前10天内接受过持续的抗血小板或抗凝治疗；

Exclusion criteria：

1. Previous intrathoracic injection of bevacizumab or PD-1/PD-L1 inhibitors; 2. Received anti-tumor therapy, including chemotherapy, thoracic radiotherapy, targeted therapy, immunotherapy, and biological therapy, within the previous 2 weeks; 3. Bilateral pleural effusion or simultaneous abdominal effusion, or simultaneous pericardial effusion; 4. Pleural effusion is encapsulated effusion or severe separation; or combined with chylothorax; or concomitant infectious pleural effusion; 5. After chest puncture/drainage in the past, there is still chest tightness and shortness of breath, which are not significantly relieved compared with before, and there are still atelectasis, pulmonary consolidation or other lung lesions that seriously affect respiratory function as determined by the investigator. 6. Known history of allergy to the drugs and components of this regimen, a history of immunodeficiency, or a history of organ transplantation; 7. Serious infection within 4 weeks before the first dose, including but not limited to comorbidities requiring hospitalization, sepsis, or severe pneumonia; Active infection with systemic anti-infective therapy within 2 weeks prior to the first dose (excluding antiviral therapy for hepatitis B or hepatitis C); 8. History of severe bleeding tendency or coagulation dysfunction; Presence of clinically significant bleeding symptoms within 4 weeks before the first dose, including but not limited to gastrointestinal bleeding, coughing up blood (defined as coughing up or coughing up 1 teaspoon of fresh blood or small blood clots≥, or only coughing up blood without sputum, those with blood in sputum are allowed to be enrolled), nasal bleeding (excluding epistaxis bleeding and retracting nasal discharge); Received continuous antiplatelet or anticoagulant therapy within 10 days before the first dose.

研究实施时间：

Study execute time：

从 From 2025-07-11 00:00:00至 To 2028-06-30 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-07-22 00:00:00 至 To 2027-06-30 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	36
Group：	Experimental group	Sample size：	36
干预措施：	符合入组标准的受试者经超声引导下胸腔置管引流且在胸腔积液完全引流后，患者接受胸腔内灌注依沃西单抗。第一阶段为安全导入期（Safety run in），先入组 3 例受试者接受胸腔内灌注依沃西单抗 300mg（溶于 50 mL 生理盐水，第 1 天、第 3 天灌注，每两周 1 周期，注射后，夹管保留 3 天，随后开放引流完全。）, 若 0/3 例发生 DLT，则升至下一剂量组（400mg）。若 1/3 例发生 DLT，则扩增至 6 例，若总 DLT≤1/6 则升高剂量至 400mg。若≥2/3 或≥2/6 例发生 DLT，则终止递增，300mg 的剂量为 RP2D。若 400mg 组，≥2/6 例 DLT，则 RP2D 定为 300mg。推荐的 II 期拓展研究的剂量（RP2D）将在安全性导入期确定。一旦确定 RP2D，患者将接受依沃西单抗的 RP2D 胸腔内灌注治疗，拓展阶段入组 30 例受试者。所有受试者同时接受标准方案下的全身系统治疗（如化疗、靶向治疗或免疫治疗），具体方案由研究者制定。	干预措施代码：
Intervention：	Subjects who meet the enrollment criteria receive intrathoracic inffusion of ivocimab after ultrasound-guided thoracic catheterization drainage and complete drainage of pleural effusion. The first stage is the safety run in, in which 3 subjects will be enrolled to receive intrathoracic perfusion of ivoximab 300mg (dissolved in 50 mL of normal saline, perfused on day 1 and day 3, 1 cycle every two weeks, after injection, the clip tube will be kept for 3 days, and then opened for complete drainage. ), if 0/3 cases have DLTs, they will be promoted to the next dose group (400mg). If 1/3 of the DLTs occurred, the dose was expanded to 6 cases, and if the total DLTs were <=1/6, the dose was increased to 400mg. If DLTs occur in >=2/3 or >=2/6 cases, the escalation is terminated and the 300 mg dose is the RP2D. If the 400mg group >= 2/6 DLTs, the RP2D will be set at 300mg. The recommended dose (RP2D) for the phase II extension study will be determined during the safety lead-in period. Once the RP2D is determined, patients will be treated with the RP2D intrathoracic perfusion of ivocimab with 30 subjects enrolled in the expansion phase. All subjects received concurrent systemic therapy (such as chemotherapy, targeted therapy, or immunotherapy) under standard protocols treatment), and the specific plan is formulated by the researcher.	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	山东省	市(区县)：
Country：	China	Province：	Shandong	City：
单位(医院)：	山东第一医科大学附属肿瘤医院（山东省肿瘤防治研究院、山东省肿瘤医院）	单位级别：	三级甲等
Institution hospital：	Shandong First Medical University and Shandong Academy of Medical Sciences (Shandong Cancer Hospital ＆Institute)	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：	ORR	Type：	Primary indicator
测量时间点：	第一次疗效评价	测量方法：	根据WHO胸腔积液疗效评价标准定义为完全缓解（CR）及部分缓解（PR）的受试者占总受试者的比例
Measure time point of outcome：	First Efficacy Evaluation	Measure method：	Objective Response Rate (ORR) per WHO Pleural Effusion Response Criteria。Defined as the proportion of subjects achieving complete response (CR) or partial response (PR) among the total study population.

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	胸腔积液	组织：
Sample Name：	Pleural Effusion	Tissue：
人体标本去向	使用后保存	说明
Fate of sample：	Preservation after use	Note：

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	75	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)：

None

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	否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)：	NA
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：	使用CRF表
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Use the CRF table
数据与安全监察委员会： Data and Safety Monitoring Committee：	无/No
注册人： Name of Registration：	2025-07-22 17:45:24