ChiCTR2000037497 版本V1.1 版本创建时间2020/10/19 08:20:01 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：

ChiCTR2000037497 

最近更新日期：

Date of Last Refreshed on：

2020-10-19 08:17:40 

注册时间：

Date of Registration：

2020-08-28 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

安罗替尼联合白蛋白结合型紫杉醇、顺铂治疗复发或转移性宫颈癌的单臂、开放、单中心的Ⅱ期临床研究

Public title：

A single arm, open, single center phase II clinical study for Anlotinib plus Albumin taxol/Cisplatin in the treatment of recurrent or metastatic cervical cancer.

注册题目简写：

English Acronym：

研究课题的正式科学名称：

安罗替尼联合白蛋白结合型紫杉醇、顺铂治疗复发或转移性宫颈癌的单臂、开放、单中心的Ⅱ期临床研究

Scientific title：

A single arm, open, single center phase II clinical study for Anlotinib plus Albumin taxol/Cisplatin in the treatment of recurrent or metastatic cervical 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：

高玉彬 

研究负责人：

高福锋 

Applicant：

GAO YUBIN 

Study leader：

GAO FUFENG 

申请注册联系人电话：

Applicant telephone：

+86 13370561519

研究负责人电话：

Study leader's telephone：

+86 0531- 67226902

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：

1362161903@qq.com

研究负责人电子邮件：

Study leader's E-mail：

gaofufeng@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：

江苏省南京市江宁区淳化街道福英路1099号1号楼

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：

1099 Fuying Road, Chunhua Street, Jiangning District, Nanjing, Jiangsu, China

Study leader's address：

440 Jiyan Road, Huaiyin District, Ji'nany, Shandong, 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：

正大天晴药业股份有限公司

Applicant's institution：

Zhengda Tianqing Pharmaceutical Group Co., Ltd

研究负责人所在单位：

山东省肿瘤医院

Affiliation of the Leader：

Shandong Cancer 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：

SDZLEC2020-054-02

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：

山东省肿瘤防治研究院伦理委员会

Name of the ethic committee：

shandong cancer prevention and treatment ethics committee

伦理委员会批准日期：

Date of approved by ethic committee：

2020-08-07 00:00:00

伦理委员会联系人：

宋现让

Contact Name of the ethic committee：

SONG XIANRANG

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：

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：

山东省肿瘤医院

Primary sponsor：

shandong cancer hospital

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 Cancer Hospital

Address：

440 Jiyan Road, Huaiyin District, Ji'nany

经费或物资来源：

医院经费

Source(s) of funding：

hospital finance

Target disease：

cervical 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：

评价安罗替尼联合静脉化疗在复发或转移性宫颈癌患者治疗中的客观缓解率（Objective Response Rate，ORR）和无进展生存期（ progression-free survival，PFS）。  

Objectives of Study：

To evaluate the ORR and PFS of Anlotinib plus chemotherapy in the treatment of recurrent or metastatic cervical 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岁，≤70岁。
2)初次治疗时经病理学确诊为宫颈鳞癌、腺鳞癌或腺癌。不包含下列少见病理类型：神经内分泌癌、透明细胞癌或肉瘤等。
3)入组患者需经组织学或影像学证实为治疗后复发或转移，且末次含铂化疗大于6个月，不适合手术或放射治疗。
4）治疗前一个月内未接受过任何形式的抗肿瘤治疗（包括：任何形式的化疗、放疗、靶向治疗及中药治疗等）。
5)至少有一个可测量病灶（根据RECIST 1.1标准，肿瘤病灶CT扫描、体格检查或妇科检查长径≥10mm，淋巴结病灶CT扫描短径≥10mm）
6)ECOG评分：0-2分；
7)预计生存期 ≥ 3月；
8)受试者接受其它治疗造成的损害已恢复，其中接受亚硝基或丝裂霉素的间隔≥6周；接受其它细胞毒性药物、放疗或手术≥4周，且伤口已完全愈合；
9)主要器官功能正常，即符合下列标准：
A血常规检查标准需符合（14天内未输血及血制品）：
a.ANC≥1.5×109/L；
b.PLT≥80×109/L；
B生化检查需符合以下标准：
a.TBIL<1.5ULN；
b.ALT和AST<2.5ULN，而对于肝转移患者则< 5ULN；
c.血清Cr≤1.25ULN或内生肌酐清除率> 45 ml/min（Cockcroft-Gault公式）；
10)有潜在生育可能的患者，需要在研究治疗期间和和研究治疗期结束后1个月内采用一种经医学认可的避孕措施（如宫内节育器、避孕药或避孕套）；并需在研究入组前的72h内血清或尿HCG检查必须为阴性，且必须为非哺乳期；
11)受试者自愿加入本研究，并签署知情同意书，依从性好，配合随访。

Inclusion criteria

1) Age: ≥18 years, ≤70 years.
2) Cervical squamous cell carcinoma, adenosquamous cell carcinoma or adenocarcinoma was pathologically confirmed at the initial treatment.The following rare pathological types of tumors are not included: micropartial adenocarcinoma, villous tubular adenocarcinoma, clear cell carcinoma or sarcoma etc.
3) The enrolled patients need to be confirmed with recurrence by histology or imaging, or the disease is in the advanced stage evaluated by the researcher.
4) The patient did not receive any anti-tumor therapies (including chemotherapy, radiotherapy and traditional Chinese medicine treatment etc.) within one month before the treatment, and the initial platinum-chemotherapy was more than 6 months.
5) At least one measurable lesion (according to RECIST 1.1, CT results of tumor lesion, physical examination or gynecological examination, long diameter ≥10mm, and CT scan of lymph node lesion, short diameter ≥10mm)
6)ECOG score: 0-2;
7) Life expectancy ≥ 3 months;
8) The subjects recovered from the damage caused by other treatments, in which they received nitroso or mitomycin at an interval of ≥6 weeks;Received other cytotoxic drug, radiotherapy or surgery ≥4 weeks, and the wound was completely healed;
9) The main organs function normally, that is, they meet the following standards:
A Blood routine examination standards shall be met (no blood transfusion or blood products received within 14 days) :
a.ANC ≥ 1.5 x 109 / L;
b.PLT ≥80 x 109 / L or higher;
B Biochemical examination shall meet the following standards:
a.TBIL＜1.5 ULN;
b.ALT and AST＜2.5ULN, patients with liver metastasis＜5ULN
c.Serum Cr≤1.25ULN or endogenous creatinine clearance rate ＞45 ml/min (Cockcroft-Gault formula);
10) Should use a medically approved contraceptive method (e.g., iUD, contraceptive pill or condom) during the treatment and within 1 month after the study in patients with potential fertility;Serum or urine HCG must be negative within 72 hours before study inclusion and must be in non-lactation period.
11) Subjects voluntarily participate in this study and sign informed consent, with good compliance and follow-up.

排除标准：

出现以下任何一项目的患者将不能入组本研究：
1）肿瘤相关症状及治疗：
①无法控制的需要反复引流的中到大量胸腔积液，腹腔积液或者心包积液；
②影像学（CT或者MRI）显示肿瘤侵犯大血管者或研究者判断后续研究期间肿瘤极有可能侵袭重要血管引起致命大出血者；
③既往接受过抗血管生成靶向药物治疗，或其他针对VEGFR抑制剂的治疗；
2）合并疾病/病史
①任何已知或可疑的自身免疫疾病的受试者，除外：仅需要激素替代疗法治疗的因自身免疫性甲状腺炎导致的甲状腺功能减退；血糖得以控制的稳定的I型糖尿病的受试者；
②高血压，且经降压药物治疗无法获得良好控制（收缩压>140 mmHg或者舒张压>90 mmHg）；随机前6个月内，出现以下情况：心肌梗死、严重/不稳定型心绞痛、NYHA 2级以上心功能不全、有临床意义的室上性或室性心律失常以及症状性充血性心力衰竭；
③存在间质性肺病、非感染性肺炎或无法控制的系统性疾病（如：糖尿病、肺纤维化和急性肺炎等）；
④首次研究用药前28天内减毒活疫苗接种史或者预计研究期间行减毒活疫苗接种；
⑤人类免疫缺陷病毒（HIV）感染或已知有获得性免疫缺陷综合征（艾滋病）；活动性肝炎（乙型肝炎，定义为HBV-DNA ≥ 500 IU/ml；丙型肝炎，定义为HCV-RNA高于分析方法的检测下限）或合并乙肝和丙肝共同感染；
⑥首次给药前4周内存在重度感染，包括但不限于需住院治疗的菌血症、重症肺炎等；或首次给药前2周内存在需使用系统抗生素治疗的CTCAE≥2级的活动性感染，或在筛选期间/首次给药前出现不明原因的发热>38.5°C（经研究者判断，因肿瘤原因导致的发热可以入组）；给药前1年内有活动性结核感染证据；
⑦进入研究前5年内曾诊断为任何其他恶性肿瘤，经充分治疗的基底细胞癌或鳞状细胞皮肤癌或宫颈原位癌除外；
⑧存在具有显著临床意义的肠梗阻；
⑨既往接受过或准备接受同种异体骨髓移植或实体器官移植的受试者；
⑩周围神经病变≥2级者；
3）出血倾向性疾病
①随机前6个月内发生的动静脉血栓事件，如脑血管意外（包括暂时性缺血性发作）、深静脉血栓（因前期化疗行静脉置管引发静脉血栓经研究者判断已痊愈者除外）及肺栓塞等；
②进入研究前2个月内出现咯鲜血症状且最大日咯血量约≥2.5 mL的受试者。进入研究前3个月内出现过显著临床意义的出血症状或具有明确的出血倾向，如消化道出血、出血性胃溃疡、基线期大便潜血++及以上，或患有脉管炎等；已知存在遗传性或获得性出血及血栓倾向，如：血友病、凝血技能障碍、血小板减少、脾功能亢进等；
③凝血功能异常（INR>1.5或APTT>1.5×ULN），具有出血倾向或正在接受溶栓或需要使用华法林或肝素长期抗凝治疗，或需要长期抗血小板治疗（阿司匹林≥300 mg/天或氯吡格雷≥75 mg/天）；
4）研究治疗相关
首次给药前4周内接受过全身免疫刺激剂治疗（包括但不限于干扰素或白细胞介素-2，包括处于临床研究阶段的免疫刺激剂）的受试者。
已知对研究药物或其任何辅料过敏；或者对其他单克隆抗体发生过严重过敏反应；
5）随机前4周内参与过任何其他药物临床研究，或距离末次研究用药不超过5个半衰期。
6）受试者已知有精神类药物滥用、酗酒或吸毒史。
7）妊娠期、哺乳期或计划在研究期间妊娠的女性受试者
8）经研究者判断，患者可能有其他可能导致本研究被迫中途终止的因素，如其他的严重疾病或严重的实验室检查异常或伴有其他会影响到受试者的安全，或试验资料及样品收集的家庭或社会等因素；

Exclusion criteria：

Patients with any of the following items will not be enrolled in this study
1) Tumor-related symptoms and treatment:
(1).Uncontrollable, medium to large pleural, peritoneal, or pericardial effusion, requiring drainage repeatly;
Imaging (CT or MRI) shows that the tumor invades the large vessels or the researchers judge that the tumor is very likely to invade the important vessels and cause fatal hemorrhage during the follow-up study;
(3) Prior to receiving anti-angiogenesis therapy, or other VEGFR inhibitors treatment;
2)Concomitant disease/history
(1)Subjects with any known or suspected autoimmune disease, except: hypothyroidism due to autoimmune thyroiditis requiring only hormone replacement therapy;Subjects with stable type 1 diabetes in which blood sugar is controlled;
(2)Hypertension, and cannot get controlled through antihypertensive drugs (systolic blood pressure＞140 mmHg or diastolic blood pressure＞90 mmHg);In the 6 months before randomization, patients with myocardial infarction, severe/unstable angina pectoris, NYHA grade 2 or above cardiac dysfunction, clinically significant supraventricular or ventricular arrhythmias, and symptomatic congestive heart failure should be exclued.
(3) Patients with interstitial lung disease, non-infectious pneumonia or uncontrollable systemic disease (e.g., diabetes mellitus, pulmonary fibrosis, acute pneumonia, etc.);
(4)Received live attenuated vaccine within 28 days before the first study or will receive live attenuated vaccine during the following study;
(5) Infected Human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS);Active hepatitis (hepatitis B, defined as HBV-DNA ≥ 500 IU/ml;Hepatitis C, defined as HCV-RNA above the detection limit) or hepatitis B and C co-infection;
(6)Severe infection occurred within 4 weeks prior to the first administration, including but not limited to bacteremia requiring hospitalization and severe pneumonia etc;Or an active CTCAE ≥2 infection requiring systemic antibiotics within 2 weeks prior to first administration; or a fever of unknown cause ＞38.5°C occurring during screening/prior to first administration (as determined by the investigator, fever caused by tumor can be included);Evidence of active TB infection within 1 year before administration;
(7)Had been diagnosed with any other malignant tumor within 5 years before entering the study, except basal cell carcinoma or squamous cell carcinoma or carcinoma in situ of the cervix after adequate treatment;
(8)There is a significant clinical significance of intestinal obstruction;
(9) subjects who have received or are about to receive allogeneic bone marrow transplantation or solid organ transplantation;
(10)peripheral neuropathy ≥2;
3）Bleeding tendency disease
(1) events of arteriovenous thrombosis (AVT) in the first 6 months of randomization, such as cerebrovascular accident (including temporary ischemic attack), deep venous thrombosis (except for venous thrombosis caused by intravenous catheterization due to previous chemotherapy and confirmed by the investigator to be cured) and pulmonary embolism etc;
(2) Subjects with cough up blood symptoms and maximum daily hemoptysis ≥ 2.5ml within 2 months before entering the study.Clinically significant bleeding symptoms or a clear bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal occult blood ++ or above at baseline, or vasculitis, were observed within 3 months before the study.Hereditary or acquired bleeding and thrombotic tendencies are known, such as hemophilia, coagulation disorders, thrombocytopenia, hypersplenism, etc.
(3) Abnormal coagulation function (INR＞1.5 or APTT＞1.5×ULN), have bleeding tendency or are receiving thrombolytic therapy or require long-term anticoagulant therapy with warfarin or heparin, or require long-term antiplatelet therapy (aspirin ≥300 mg/ d or clopidogrel ≥75 mg/ d);
4）Research treatment related
Subjects who received systemic immunostimulants (including but not limited to interferon or interleukin-2, including immunostimulants in clinical studies) within 4 weeks prior to first administration.
Known allergy to the study drug or any of its excipients;Or had a serious allergic reaction to other monoclonal antibodies;
5）Randomized to participate in any other drug clinical study within the first 4 weeks, or not more than 5 half-lives from the last study.
6）The subject has a known history of psychotropic substance abuse, alcohol or drug abuse.
7）Female subjects who are pregnant, breastfeeding, or planning to be pregnant during the study period
8）According to the judgment of the researcher, the patient may have other factors that may lead to the forced termination of the study, such as other serious diseases or abnormal laboratory tests, or other factors that may affect the safety of the subjects, or family or social factors such as the collection of test data and samples;

研究实施时间：

Study execute time：

从 From 2020-09-01 00:00:00至 To 2021-09-01 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2020-12-01 00:00:00 至 To 2022-09-01 00:00:00  

干预措施：

Interventions：

组别：

Case series

样本量：

59

Group：

Case series

Sample size：

干预措施：

安罗替尼联合白蛋白紫杉醇/顺铂

干预措施代码：

Intervention：

Anlotinib plus Albumin taxol/cisplatin

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)：

山东省肿瘤医院 

单位级别：

三甲医院 

Institution
hospital：

Shandong Cancer Hospital

Level of the institution：

Tertiary A Hospital

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：

PFS

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

研究者评估的客观缓解

指标类型：

主要指标

Outcome：

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：

总体生存期

指标类型：

次要指标

Outcome：

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：

疾病控制率

指标类型：

次要指标

Outcome：

DCR

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 70 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）：

试验为非随机

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

This trial is non-randomization

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

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）：

发表文章或学术会议报告

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

Publish articles or academic conference reports

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：

病历记录表和电子采集和管理系统

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

Case Record Form,CRF and Electronic Data Capture,EDC

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2020-08-28 11:18:59