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：	ChiCTR2400091168
最近更新日期： Date of Last Refreshed on：	2024-10-22 16:01:38
注册时间： Date of Registration：	2024-10-22 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	多柔比星脂质体联合普特利单抗新辅助治疗未分化多形性肉瘤和粘液纤维肉瘤的前瞻性、单臂、单中心临床研究
Public title：	A prospective, single-arm, single-center clinical study of neoadjuvant doxorubicin liposome combined with pucotenlimab in the treatment of undifferentiated pleomorphic sarcoma and myxofibrosarcoma
注册题目简写：	多柔比星脂质体联合普特利单抗新辅助治疗未分化多形性肉瘤和粘液纤维肉瘤的临床研究
English Acronym：	Clinical study of neoadjuvant doxorubicin liposome combined with pucotenlimab in the treatment of undifferentiated pleomorphic sarcoma and myxofibrosarcoma
研究课题的正式科学名称：	多柔比星脂质体联合普特利单抗新辅助治疗未分化多形性肉瘤和粘液纤维肉瘤的前瞻性、单臂、单中心临床研究
Scientific title：	A prospective, single-arm, single-center clinical study of neoadjuvant doxorubicin liposome combined with pucotenlimab in the treatment of undifferentiated pleomorphic sarcoma and myxofibrosarcoma
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：	张浩	研究负责人：	杨诚
Applicant：	Hao Zhang	Study leader：	Cheng Yang
申请注册联系人电话： Applicant telephone：	+86 153 1790 8178	研究负责人电话： Study leader's telephone：	+86 186 0177 0909
申请注册联系人传真： Applicant Fax：	+86 021-81885667	研究负责人传真： Study leader's fax：	+86 021-81885667
申请注册联系人电子邮件： Applicant E-mail：	2970514180@qq.com	研究负责人电子邮件： Study leader's E-mail：	ddyc2001@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：	中国上海市黄浦区凤阳路415号	研究负责人通讯地址：	中国上海市黄浦区凤阳路415号
Applicant address：	415 Fengyang Road, Huangpu District, Shanghai, China	Study leader's address：	415 Fengyang Road, Huangpu District, Shanghai, 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：	上海长征医院
Applicant's institution：	Shanghai Changzheng hospital
研究负责人所在单位：	上海长征医院
Affiliation of the Leader：	Shanghai Changzheng hospital

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：	2024SL132	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：	上海长征医院生物医学研究伦理委员会
Name of the ethic committee：	Shanghai Changzheng Hospital Biomedical Research Ethics Committee
伦理委员会批准日期： Date of approved by ethic committee：	2024-10-10 00:00:00
伦理委员会联系人：	孙吕平
Contact Name of the ethic committee：	Sun Lvping
伦理委员会联系地址：	中国上海市黄浦区凤阳路415号
Contact Address of the ethic committee：	415 Fengyang Road, Huangpu District, Shanghai, China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 21 8188 5046	伦理委员会联系人邮箱： Contact email of the ethic committee：	shczkykxs@163.com

研究实施负责（组长）单位：

上海长征医院

Primary sponsor：

Shanghai Changzheng hospital

研究实施负责（组长）单位地址：

中国上海市黄浦区凤阳路415号

Primary sponsor's address：

415 Fengyang Road, Huangpu District, Shanghai, 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)：	市辖区	市(区县)：	市辖区
Country：	China	Province：	Shanghai	City：
单位(医院)：	上海长征医院	具体地址：	中国上海市黄浦区凤阳路415号
Institution hospital：	Shanghai Changzheng hospital	Address：	415 Fengyang Road, Huangpu District, Shanghai, China

经费或物资来源：

NO

Source(s) of funding：

None

研究疾病：

未分化多形性肉瘤和粘液纤维肉瘤

Target disease：

Undifferentiated pleomorphic sarcoma and myxofibrosarcoma

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：

研究目的 − 采用客观缓解率评估多柔比星脂质体联合普特利单抗新辅助治疗未分化多形性肉瘤和粘液纤维肉瘤患者的疗效和安全性。 − 1、根据RECIST（1.1版）标准评价多柔比星脂质体联合普特利单抗新辅助治疗未分化多形性肉瘤和粘液纤维肉瘤患者12周的客观缓解率（Objective Response Rate，ORR）。 − 2、根据药物常见不良事件评价标准（CTCAE-V5.0）评估多柔比星脂质体联合普特利单抗新辅助治疗未分化多形性肉瘤和粘液纤维肉瘤患者的安全性和耐受性。次要目的： − 采用主要病理缓解率（MPR）、无事件生存期（EFS）、总生存期（OS）评估多柔比星脂质体联合普特利单抗新辅助治疗未分化多形性肉瘤和粘液纤维肉瘤患者的疗效。

Objectives of Study：

Research purpose: Objective response rates were used to evaluate the efficacy and safety of doxorubicin liposomes combined with putrelizumab neoadjuvant therapy in patients with undifferentiated pleurosarcoma and myxosarcoma. − 1. To evaluate the 12-week Objective Response Rate (ORR) of doxorubicin liposomes combined with Putrelizumab neoadjuvant therapy for undifferentiated pleurosarcoma and myxosarcoma according to RECIST (version 1.1) criteria. − 2. To evaluate the safety and tolerability of doxorubicin liposomes combined with putrelizumab neoadjuvant therapy in patients with undifferentiated pleurosarcoma and myxosarcoma according to the evaluation criteria for common Adverse Events (CTCAE-V5.0). Secondary purpose: − Major pathological response rate (MPR), event-free survival (EFS), and overall survival (OS) were used to evaluate the efficacy of doxorubicin liposomes combined with putrelizumab neoadjuvant therapy in patients with undifferentiated pleurosarcoma and myxosarcoma.

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. Have fully understood the study and voluntarily signed the informed consent;
2. Age 18-75 years old (inclusive), male and female;
3. Pathologically and/or cytologically confirmed undifferentiated pleomorphic sarcoma or myxofibrosarcoma with a tumor diameter greater than 5 cm, or with a tumor diameter less than 5 cm but with difficult resection of stage 1 R0, which is not expected to achieve satisfactory surgical margins or may cause serious functional impairment;
4. Have not received anti-tumor therapy such as chemotherapy, targeted therapy, immunotherapy and local radiotherapy;
5. Have at least one measurable lesion according to RECIST (V1.1) criteria;
6. The physical status score of Eastern Tumor Collaboration Group (ECOG) was 0-2 points;
7. Major organ function meets the following criteria before treatment (no blood transfusion, EPO, G-CSF, etc., within 14 days before screening period) :
Blood routine: absolute neutrophil count ≥ 1.5 × 109 /L; Platelet ≥ 100 × 109 /L; Hemoglobin ≥ 90g/L;
Renal function: serum creatinine ≤ 1.5 × upper limit of normal range (ULN);
Liver function: total bilirubin ≤ 1.5 ×ULN (patients with liver metastasis, bile duct obstruction or confirmed Gilbert syndrome: ≤ 3×ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (liver metastases: ≤ 5 × ULN);
Coagulation function: International standardized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN; Partially activated thromboplastin time (APTT) : ≤ 1.5 × ULN;
8. Expected survival ≥3 months;
9. Women of childbearing age must have a negative pregnancy test (serum or urine) within 7 days prior to enrollment; Both men and women were required to voluntarily use effective contraception during the study period.

排除标准：

1. 合并其他恶性肿瘤（若已结束抗肿瘤治疗且2年内未见肿瘤复发及转移，可纳入本研究）； 2. 在首次使用研究药物前 4 周内进行过大型外科手术或尚未从之前任何有创性操作中完全恢复； 3. 在首次使用研究药物前 2 周内接受过全身使用的糖皮质激素（强的松＞10mg/天或等效剂量的同类药物）或其他免疫抑制剂治疗［除外以下情况：使用局部、眼部、关节腔内、鼻内和吸入型糖皮质激素治疗；短期使用糖皮质激素进行预防治疗（例如预防造影剂过敏）］； 4. 入组前 2 周内有感染，且需要全身（口服或 IV）抗感染治疗（无并发症的尿路感染或上呼吸道感染除外）； 5. 在首次使用研究药物前 4 周内使用过灭活疫苗或减毒活疫苗或新型冠状病毒疫苗； 6. 伴有严重的内科疾病，例如：Ⅲ级及以上心功能异常（NYHA标准）、缺血性心脏病（如心肌梗死或心绞痛）等心血管疾病，控制不佳的糖尿病（空腹血糖≥10 mmol/L），控制不佳的高血压（收缩压>140 mmHg和/或舒张压>90 mmHg），超声心动图显示射血分数<50%等； 7. 肿瘤有明确且活动的脑转移病灶； 8. 有胸/腹水或心包积液并伴有临床症状或需要对症处理者； 9. 有严重肺部疾病史的患者，如间质性肺疾病和/或肺炎，或肺动脉高压，或既往存在肺功能严重受损； 10. 甲状腺功能异常患者，但如果经药物控制后甲状腺功能正常，则允许入组； 11. 活动性乙型肝炎、活动性丙型肝炎病毒感染或活动性梅毒感染。活动性乙型肝炎：乙肝表面抗原（HBsAg）阳性，且 HBV-DNA 定量滴度检测 ≥ 2000IU/mL。若 HBsAg 阳性，且外周血 HBV-DNA < 2000IU/mL，如果研究者认为受试者慢性乙肝处于稳定期且不会增加受试者风险，则受试者有资格入选；活动性丙型肝炎：抗 HCV 阳性且 HCV RNA 阳性；活动性梅毒感染：梅毒螺旋体抗体（RPR 或 TRUST）阳性或存在需要系统性治疗的梅毒感染； 12. 有自身免疫性疾病史（除外结节性硬化）、免疫缺陷病史，包括 HIV 检测阳性，或患有其他获得性、先天性免疫缺陷疾病，或有器官移植史； 13. 经研究者判断认为有严重的危害患者安全、影响患者完成研究的伴随疾病（如不可控的高血压、活动性胃肠道出血等）或存在其他原因而不适合参加本临床研究者。

Exclusion criteria：

1. Complicated with other malignant tumors (patients who have finished anti-tumor therapy and no tumor recurrence or metastasis within 2 years can be included in this study); 2. Had a major surgical procedure or had not fully recovered from any previous invasive procedure within 4 weeks prior to the first use of the study drug; 3. Received systemic use of glucocorticoids (prednisone > 10mg/ day or equivalent dose of the same drug) or other immunosuppressants within 2 weeks prior to the first use of the study drug (except for the following: Treatment with topical, ocular, intraarticular, intranasal and inhaled glucocorticoids; short-term use of glucocorticoids for preventive treatment (e.g. to prevent hypersensitivity to contrast media)]; 4. Had infection within 2 weeks prior to enrollment and required systemic (oral or IV) anti-infective therapy (except for uncomplicated urinary tract infections or upper respiratory tract infections); 5. Use of inactivated or live attenuated vaccine or novel coronavirus vaccine within 4 weeks prior to the first use of the investigational drug; 6. Accompanied by serious medical problems, such as: Cardiovascular diseases such as grade III and above cardiac dysfunction (NYHA criteria), ischemic heart disease (e.g., myocardial infarction or angina), poorly controlled diabetes (fasting blood glucose ≥10 mmol/L), poorly controlled hypertension (systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg), Echocardiography showed that ejection fraction was less than 50%. 7. The tumor has clear and active brain metastases; 8. Patients with chest/ascites or pericardial effusion accompanied by clinical symptoms or need symptomatic treatment; 9. Patients with a history of serious lung disease, such as interstitial lung disease and/or pneumonia, or pulmonary hypertension, or a history of severely impaired lung function; 10. Patients with abnormal thyroid function, but if the thyroid function is normal after drug control, they are allowed to enter the group; 11. Active hepatitis B, active hepatitis C virus infection or active syphilis infection. Active hepatitis B: Hepatitis B surface antigen (HBsAg) positive and HBV-DNA quantitative titer ≥ 2000IU/mL. If HBsAg is positive, HBV-DNA in peripheral blood is < 2000IU/mL, and if the investigator believes that the subject's chronic hepatitis B is stable and does not increase the risk of the subject, the subject is eligible for enrollment. Active hepatitis C: anti-HCV positive and HCV RNA positive; Active syphilis infection: positive for treponema pallidum antibodies (RPR or TRUST) or the presence of a syphilis infection that requires systemic treatment; 12. A history of autoimmune diseases (other than tuberous sclerosis), a history of immunodeficiency, including HIV testing positive, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; 13. According to the judgment of the researcher, the patient is not eligible to participate in this clinical study because of concomitant diseases (such as uncontrollable hypertension, active gastrointestinal bleeding, etc.) or other reasons that seriously endanger the safety of the patient and affect the completion of the study.

研究实施时间：

Study execute time：

从 From 2024-10-10 00:00:00至 To 2028-10-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2024-10-22 00:00:00 至 To 2026-10-31 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	22
Group：	Experimental group	Sample size：	22
干预措施：	术前治疗：多柔比星脂质体，50mg/m2，静脉滴注，每3周1次。在上述化疗方案基础上加用普特利单抗，治疗方案为：200mg，静脉滴注，每3周1次。术后治疗：术后 14-21 天进行相关检查，排除治疗禁忌后开始术后治疗。术后化疗由主要研究者根据指南决定治疗方案；同时联合为期一年的免疫维持治疗，治疗的起始时间从首次普特利单抗用药开始计算。	干预措施代码：
Intervention：	Preoperative treatment: Doxorubicin liposomes, 50mg/m2, intravenously, once every 3 weeks. On the basis of the above chemotherapy regimen, Ptrelizumab was added to the treatment regimen: 200mg intravenously, once every 3 weeks. Postoperative treatment: Relevant examinations were performed 14-21 days after surgery, and postoperative treatment was started after treatment contraindications were excluded. Postoperative chemotherapy was determined by the principal investigator according to the guidelines. In combination with one year of immunomaintenance therapy, the time of treatment initiation was calculated from the first dose of ptolizumab.	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	上海	市(区县)：	市辖区
Country：	China	Province：	Shanghai	City：	Municipal district
单位(医院)：	上海长征医院	单位级别：	三甲
Institution hospital：	Shanghai Changzheng Hospital	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	Type：	Primary indicator
测量时间点：	治疗12周后	测量方法：	RECIST（1.1版）标准
Measure time point of outcome：	After 12 weeks of treatment	Measure method：	RECIST (version 1.1) standard

指标中文名：	主要病理缓解率	指标类型：	次要指标
Outcome：	Major pathological response rate	Type：	Secondary indicator
测量时间点：	手术后	测量方法：	组织病理学评估
Measure time point of outcome：	postoperation	Measure method：	Histopathological evaluation

指标中文名：	无事件生存期	指标类型：	次要指标
Outcome：	Event-free survival	Type：	Secondary indicator
测量时间点：	定期随访	测量方法：	研究者评估
Measure time point of outcome：	Regular follow-up	Measure method：	Assessments BY INVESTIGATORS

指标中文名：	总生存期	指标类型：	次要指标
Outcome：	Overall Survaval	Type：	Secondary indicator
测量时间点：	定期随访	测量方法：	研究者评估
Measure time point of outcome：	Regular follow-up	Measure method：	Assessments BY INVESTIGATORS

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	肿瘤组织	组织：
Sample Name：	Tumor tissue	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:

公开/Public

盲法：
Blinding：
试验完成后的统计结果（上传文件）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

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)：	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：	access
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	access
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：	2024-10-22 16:01:32