ChiCTR2500111824 版本V1.0 版本创建时间2025/11/06 14:56:34 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：

ChiCTR2500111824 

最近更新日期：

Date of Last Refreshed on：

2025-11-06 14:56:22 

注册时间：

Date of Registration：

2025-11-06 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

依托泊苷胶囊联合贝伐珠单抗及艾帕洛利托沃瑞利单抗治疗铂类耐药或铂类难治性卵巢癌的单臂、开放、单中心、探索性临床Ⅱ期研究

Public title：

A single-arm, open-label, single-center, exploratory phase II clinical study of etoposide capsules combined with bevacizumab and avelumab in the treatment of platinum-resistant or platinum-refractory ovarian cancer

注册题目简写：

English Acronym：

研究课题的正式科学名称：

依托泊苷胶囊联合贝伐珠单抗及艾帕洛利托沃瑞利单抗治疗铂类耐药或铂类难治性卵巢癌的单臂、开放、单中心、探索性临床Ⅱ期研究

Scientific title：

A single-arm, open-label, single-center, exploratory phase II clinical study of etoposide capsules combined with bevacizumab and avelumab in the treatment of platinum-resistant or platinum-refractory ovarian 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：

居杏珠 

研究负责人：

居杏珠 

Applicant：

Xingzhu Ju  

Study leader：

Xingzhu Ju 

申请注册联系人电话：

Applicant telephone：

+86 138 1731 3189

研究负责人电话：

Study leader's telephone：

+86 138 1731 3189

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：

B5012@163.com

研究负责人电子邮件：

Study leader's E-mail：

B5012@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：

上海市徐汇区东安路270号

研究负责人通讯地址：

上海市徐汇区东安路270号

Applicant address：

No.270 Dongan Road, Xuhui District. Shanghai City

Study leader's address：

No.270 Dongan Road, Xuhui District. Shanghai City

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：

复旦大学附属肿瘤医院

Applicant's institution：

Fudan University Shanghai Cancer Center

研究负责人所在单位：

复旦大学附属肿瘤医院

Affiliation of the Leader：

Fudan University Shanghai Cancer Center

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：

2508327-6

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：

复旦大学附属肿瘤医院医学伦理委员会

Name of the ethic committee：

Medical Ethics Committee of Fudan University Shanghai Cancer Center

伦理委员会批准日期：

Date of approved by ethic committee：

2025-08-25 00:00:00

伦理委员会联系人：

张玮静

Contact Name of the ethic committee：

Weijing Zhang

伦理委员会联系地址：

上海市徐汇区东安路270号

Contact Address of the ethic committee：

No.270 Dongan Road, Xuhui District. Shanghai City

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 34778299

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：

复旦大学附属肿瘤医院

Primary sponsor：

Fudan University Shanghai Cancer Center

研究实施负责（组长）单位地址：

上海市徐汇区东安路270号

Primary sponsor's address：

No.270 Dongan Road, Xuhui District. Shanghai City

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

上海

市(区县)：

Country：

China

Province：

Shanghai

City：

单位(医院)：

复旦大学附属肿瘤医院

具体地址：

上海市徐汇区东安路270号

Institution
hospital：

Fudan University Shanghai Cancer Center

Address：

No.270 Dongan Road, Xuhui District. Shanghai City

经费或物资来源：

自选课题（自筹）

Source(s) of funding：

Self-raised funds

Target disease：

Ovarian cancer

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：

观察和评价依托泊苷胶囊联合贝伐珠单抗及艾帕洛利托沃瑞利单抗治疗铂类耐药或铂类难治性卵巢癌的有效性和安全性。  

Objectives of Study：

To observe and evaluate the efficacy and safety of etoposide capsules combined with bevacizumab and avelumab in the treatment of platinum-resistant or platinum-refractory ovarian cancer.

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：18-75，女性； 2.根据 RECIST 1.1 标准，基线有可测量病灶； 3.ECOG PS： 0-1； 4.铂耐药或铂难治复发的上皮性卵巢、输卵管、原发腹膜癌；提供10张白片用于病理类型确认及疗效标志物探索，且满足以下所有条件。 （1）接受过≥1线且≤6线的全身性治疗，其中铂耐药复发后仅接受过≤4线的全身性治疗。 （2）既往治疗中应包括至少1种含铂化疗方案。具体分为以下两种情况： a.对于既往只接受过1线含铂化疗的患者，必须达到疾病缓解(CR或PR)，然后在末次含铂化疗结束后≥4周且＜6个月的时间段内出现疾病进展。 b.对于既往接受过2至5线全身治疗的患者，要求必须在末次含铂化疗结束后＜6个月的时间段内疾病进展。 注：线数判断需要注意以下要求： 新辅助±辅助全身治疗整体算为一个线数。 维持治疗不单独计算线数。 单纯内分泌治疗算为一个线数，但因非疾病进展（如仅CA-125升高）而使用内分泌治疗不算线数。 在没有疾病进展的情况下因不耐受改变治疗方案不算为换线。 受试者需在最后一次全身治疗后出现疾病进展。 5.主要器官功能良好，符合下列标准： a.血常规检查（14 天内未输血、未使用造血刺激因子类药物纠正状态下）：血红蛋白（Hb）≥90g/L；绝对中性粒细胞计数（ANC）≥1.5×109/L；血小板（PLT）≥90×109/L；b.生化检查：谷丙转氨酶（ALT）及谷草转氨酶（AST）≤ 2.5×ULN（肿瘤肝脏转移者，≤ 5×ULN）；血清总胆红素（TBIL）≤1.5×ULN（Gilbert综合症受试者，≤ 3×ULN）；血清肌酐（Cr）≤1.5×ULN，或肌酐清除率≥60mL/min； c.凝血功能：活化部分凝血活酶时间（APTT）、国际标准化比值（INR）、凝血酶原时间（PT）≤1.5×ULN；d.尿常规检查示尿蛋白<2+；若尿蛋白≥2+，24 小时尿蛋白定量应<1 g；e.多普勒超声评估：左室射血分数 (LVEF)≥50%。 6.非手术绝育或育龄期女性患者，需要在研究治疗期间和研究治疗期结束后3个月内采用两种经医学认可的避孕措施（如宫内节育器，避孕药或避孕套）；非手术绝育的育龄期女性患者在首次用药前72h内血清HCG检查必须为阴性，而且必须为非哺乳期；对于伴侣为育龄期妇女的男性患者，应在研究治疗期间和研究治疗期结束后3个月内采用两种有效方法避孕。 7.受试者自愿加入本研究，签署知情同意书，依从性好，配合随访。

Inclusion criteria

1.Age: 18-75, female; 2.According to RECIST 1.1 criteria, there are measurable lesions at baseline; 3.ECOG PS: 0-1; 4.Platinum-resistant or platinum-refractory recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer; 10 white slides are provided for pathological type confirmation and exploration of efficacy markers, and all of the following conditions must be met. (1)Received >=1 and <=6 lines of systemic treatment, and only <=4 lines of systemic treatment after platinum-resistant recurrence. (2)At least one platinum-based chemotherapy regimen should be included in the previous treatment. Specifically, it is divided into the following two situations:For patients who have only received 1 line of platinum-based chemotherapy, they must have achieved disease remission (CR or PR), and then experienced disease progression within >=4 weeks and <6 months after the last platinum-based chemotherapy.For patients who have received 2 to 5 lines of systemic treatment, disease progression must occur within <6 months after the last platinum-based chemotherapy. Note: The determination of the number of lines should pay attention to the following requirements: Neoadjuvant ± adjuvant systemic treatment is counted as one line. Maintenance treatment is not counted as a separate line. Simple endocrine therapy is counted as one line, but endocrine therapy used due to non-disease progression (such as only elevated CA-125) is not counted as a line. Changing the treatment plan due to intolerance without disease progression is not counted as a line change. The subject must experience disease progression after the last systemic treatment. 5.Good function of major organs, meeting the following standards:Blood routine test (without blood transfusion or correction with hematopoietic stimulating factor drugs within 14 days): Hemoglobin (Hb) >= 90g/L; Absolute neutrophil count (ANC) >= 1.5×10^9/L; Platelet (PLT) >= 90×10^9/L;Biochemical test: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5×ULN (for patients with liver metastasis from tumors, <= 5×ULN); Serum total bilirubin (TBIL) <= 1.5×ULN (for Gilbert syndrome patients, <= 3×ULN); Serum creatinine (Cr) <= 1.5×ULN, or creatinine clearance rate >= 60mL/min;Coagulation function: Activated partial thromboplastin time (APTT), international normalized ratio (INR), prothrombin time (PT) <= 1.5×ULN;Urine routine test shows urine protein <2+; if urine protein >=2+, 24-hour urine protein quantification should be <1 g;Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF) >= 50%. 6.Non-surgically sterilized or women of childbearing age must use two medically approved contraceptive methods (such as intrauterine devices, contraceptives, or condoms) during the study treatment period and within 3 months after the end of the study treatment. For non-surgically sterilized women of childbearing age, the serum HCG test must be negative within 72 hours before the first dose, and they must not be lactating. For male patients whose partners are of childbearing age, two effective contraceptive methods must be used during the study treatment period and within 3 months after the end of the study treatment. 7.The subject voluntarily participates in this study, signs the informed consent form, has good compliance, and cooperates with follow-up.

排除标准：

1.同时参加其它临床试验的患者； 2.过敏体质，包括严重药物过敏或药物过敏反应史；已知对研究药物过敏或不耐受； 3.无可测量病灶或病灶不可评估者 ； 4.受试者有未经治疗的中枢神经系统转移，既往接受过系统性、根治性脑或脑膜转移治疗（放疗或手术），如影像学证实稳定已维持至少1个月，且已停止全身性激素治疗（剂量>10mg/天泼尼松或其他等疗效激素）大于2周、无临床证状的患者可以纳入； 5.无法正常吞咽药片，或存在胃肠功能异常，经研究者判断可能影响药物吸收者； 6.近期（3个月以内）发生过肠梗阻者； 7.目前存在不能控制的恶性胸水、腹水或心包积液（定义为经研究者判断不能通过利尿剂或者穿刺的方法得到有效控制）； 8.患有未经控制的合并症，包括但不限于：活动性 HBV 或 HCV 感染；已知 HIV 感染或 AIDS 病史；活动性梅毒；活动性结核病；活动性感染；未能控制的高血压、症状性心功能不全；活动性出血； 9.在研究初次给药前5年内有骨髓增生异常综合征（MDS）/急性髓系白血病（AML）或其他恶性肿瘤病史（完全缓解的原位癌和研究者确定进展缓慢的恶性肿瘤除外） 10.过往（5年内）或同时患有其它未治愈的恶性肿瘤，对于已治愈的皮肤基底细胞癌、宫颈原位癌及完成根治术后无复发>3年的乳腺癌除外； 11.妊娠期或哺乳期妇女； 12.经研究者判断，受试者有其他可能导致本研究被迫中途终止的因素，如其他的严重疾病（含精神疾病）需要合并治疗，有严重的实验室检查异常，伴有家庭或社会等因素，会影响到受试者的安全，或资料及样品的收集。

Exclusion criteria：

1.Patients who are participating in other clinical trials simultaneously; 2.Individuals with allergic constitution, including a history of severe drug allergy or drug allergic reaction; known allergy or intolerance to the study drug; 3.Patients without measurable lesions or whose lesions are unassessable; 4.Subjects with untreated central nervous system metastasis, who have previously received systemic, radical brain or meningeal metastasis treatment (radiotherapy or surgery), as long as the condition is confirmed stable by imaging and has been maintained for at least 1 month, and have stopped systemic hormone therapy (dose > 10mg/day prednisone or other equivalent efficacy hormones) for more than 2 weeks, without clinical symptoms, can be included; 5.Patients who have difficulty swallowing pills or have abnormal gastrointestinal function, as determined by the investigator, which may affect drug absorption; 6.Patients who have experienced intestinal obstruction in the recent 3 months; 7.Patients currently have uncontrollable malignant pleural effusion, ascites or pericardial effusion (defined as those that cannot be effectively controlled by diuretics or puncture methods as determined by the investigator); 8.Patients with uncontrolled comorbidities, including but not limited to: active HBV or HCV infection; known HIV infection or AIDS history; active syphilis; active tuberculosis; active infection; uncontrolled hypertension, symptomatic heart failure; active bleeding; 9.Within 5 years before the initial administration of the study drug, has a history of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or other malignant tumors (except for complete remission of in situ carcinoma and malignant tumors determined by the investigator to have a slow progression); 10.Has previously (within 5 years) or concurrently has other untreated malignant tumors, except for cured skin basal cell carcinoma, cervical in situ carcinoma and breast cancer that has completed radical surgery and has no recurrence for more than 3 years; 11.Pregnant or lactating women; 12.As determined by the investigator, the subject has other factors that may lead to the study being prematurely terminated, such as other severe diseases (including mental disorders) that require combined treatment, severe laboratory abnormalities, factors related to family or society that may affect the safety of the subject, or the collection of data and samples.

研究实施时间：

Study execute time：

从 From 2025-09-01 00:00:00至 To 2027-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2025-11-30 00:00:00 至 To 2027-12-31 00:00:00  

干预措施：

Interventions：

组别：

试验组

样本量：

33

Group：

Experimental group

Sample size：

干预措施：

依托泊苷胶囊联合贝伐珠单抗及艾帕洛利托沃瑞利单抗

干预措施代码：

Intervention：

Etoposide Capsules combined with Bevacizumab and Epalrestatolovirilumab

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)：

  

Country：

China 

Province：

Shanghai 

City：

 

单位(医院)：

复旦大学附属肿瘤医院 

单位级别：

三甲 

Institution
hospital：

Fudan University Shanghai Cancer Center

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

无进展生存期

指标类型：

主要指标

Outcome：

Progression free survival

Type：

Primary 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

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

客观反应率

指标类型：

次要指标

Outcome：

Objective remission rate

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

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：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

不良反应

指标类型：

副作用指标

Outcome：

Adverse reaction

Type：

Adverse events

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

免疫相关因子变化

指标类型：

附加指标

Outcome：

Changes in immune-related factors

Type：

Additional indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

生物标志物

指标类型：

附加指标

Outcome：

Biomarker

Type：

Additional 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 75 岁 years

性别：

女性

Gender：

Female

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：

无

Blinding：

None

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

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：

病例记录表，我们通过医院内部共建的数据库进行数据的记录，管理与保存

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

The database constructed by the hospital techniques will be used to manage and preserve the clinical data.

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：

  2025-11-06 14:56:22