ChiCTR2400089617 版本V1.0 版本创建时间2024/09/11 18:03:15 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：

 ChiCTR2400089617 

最近更新日期：

Date of Last Refreshed on：

 2024-09-11 18:03:03 

注册时间：

Date of Registration：

 2024-09-11 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

盐酸安罗替尼联合放化疗治疗局部晚期宫颈癌的开放、单臂、探索性临床研究

Public title：

An open, single-arm, exploratory clinical trial of anlotinib hydrochloride combined with chemoradiotherapy for the treatment of locally advanced cervical cancer

注册题目简写：

English Acronym：

研究课题的正式科学名称：

盐酸安罗替尼联合放化疗治疗局部晚期宫颈癌的 开放、单臂、探索性临床研究

Scientific title：

An open, single-arm, exploratory clinical trial of anlotinib hydrochloride combined with chemoradiotherapy for the treatment of locally advanced 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：

朱宝玉 

研究负责人：

高力英 

Applicant：

Zhu baoyu 

Study leader：

Gao Liying 

申请注册联系人电话：

Applicant telephone：

 +86 188 9384 8708

研究负责人电话：

Study leader's
telephone：

+86 139 9316 2152

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：

 1170656866@qq.com

研究负责人电子邮件：

Study leader's E-mail：

 1170656866@qq.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：

甘肃省兰州市安宁区刘家堡街道莫高大道999号

研究负责人通讯地址：

甘肃省兰州市安宁区刘家堡街道莫高大道999号

Applicant address：

No. 999, Mogao Avenue, Liujiabao Street, Anning District, Lanzhou City, Gansu Province

Study leader's address：

No. 999, Mogao Avenue, Liujiabao Street, Anning District, Lanzhou City, Gansu Province

申请注册联系人邮政编码：

Applicant postcode：

 710000

研究负责人邮政编码：

Study leader's postcode：

 710000

申请人所在单位：

甘肃省妇幼保健院/甘肃省中心医院

Applicant's institution：

Gansu Provincial Maternal and Child Health Care Hospital/Gansu Provincial Central Hospital

研究负责人所在单位：

甘肃省妇幼保健院/甘肃省中心医院

Affiliation of the Leader：

Gansu Provincial Maternal and Child Health Care Hospital/Gansu Provincial Central 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：

 (2024)GSFY伦审[64]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：

甘肃省妇幼保健院（甘肃省中心医院）伦理委员会

Name of the ethic committee：

Ethics Committee of Gansu Provincial Maternal and Child Health Care Hospital (Gansu Provincial Central Hospital).

伦理委员会批准日期：

Date of approved by ethic committee：

 2024-07-29 00:00:00

伦理委员会联系人：

李京文

Contact Name of the ethic committee：

Li Jingwen

伦理委员会联系地址：

甘肃省兰州市七里河区建兰路街道北街143号

Contact Address of the ethic committee：

No. 143, North Street of Jianlan Road Street, Qilihe District, Lanzhou City, Gansu Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 931 518 8871

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：

甘肃省妇幼保健院/甘肃省中心医院

Primary sponsor：

Gansu Provincial Maternal and Child Health Care Hospital/Gansu Provincial Central Hospital

研究实施负责（组长）单位地址：

甘肃省兰州市安宁区刘家堡街道莫高大道999号

Primary sponsor's address：

No. 999, Mogao Avenue, Liujiabao Street, Anning District, Lanzhou City, Gansu 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)：

甘肃

市(区县)：

兰州市

Country：

China

Province：

gansu

City：

lanzhou

单位(医院)：

甘肃省妇幼保健院/甘肃省中心医院

具体地址：

甘肃省兰州市安宁区刘家堡街道莫高大道999号

Institution
hospital：

Gansu Provincial Maternal and Child Health Care Hospital/Gansu Provincial Central Hospital

Address：

No. 999, Mogao Avenue, Liujiabao Street, Anning District, Lanzhou City, Gansu Province

经费或物资来源：

自筹

Source(s) of funding：

Self-funded

研究疾病：

宫颈癌  

Target disease：

Cervical 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：

评价盐酸安罗替尼联合放化疗治疗局部晚期宫颈癌患者的有效性及安全性  

Objectives of Study：

To assess the efficacy and safety of anlotinib hydrochloride combined with chemoradiotherapy in patients with locally advanced 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：

患者必须满足以下所有入选标准才可入组本研究： 1. 受试者自愿加入本研究，签署知情同意书，依从性好，配合访问 2. 年龄≥18岁（以签署知情同意当日计算） 3. 经病理学或组织学确诊为宫颈癌，包括鳞癌，腺癌，腺鳞癌，小细胞神经内分泌癌，且具有可测量病灶患者 4. 包括下列患者拟接受同步放化疗治疗的局部晚期患者，FIGO分期为ⅢC-ⅣA期 5. ECOG评分为0-2分 6. 预期生存期＞3个月 7. 可耐受本研究方案，器官功能良好，可参考以下： a）中性粒细胞计数≥1500/μL b）白细胞计数≥3000/mm3 c）血小板≥100,000/μL d）血红蛋白≥10g/dL e）血清肌酐≤1.5倍正常值上限，或肌酐清除率≥60mL/min (按照Cockcroft-Gault公式计算） f）总胆红素≤1.5倍正常值上限或直接胆红素≤1.0倍正常值上限 g）AST及ALT≤2.5倍正常值上限，肝转移存在时必须≤5倍正常值上限 h）血清钙≤2.5倍正常值上限 i）尿蛋白＜1000mg（24小时尿液收集） 8. 入组时妊娠检查结果为阴性，且承诺从研究开始到研究结束期间，以及最后一次给予研究用药后3个月内采取充分有效的避孕措施或禁欲的育龄期女性可入组本研究。

Inclusion criteria

Patients must meet all of the following inclusion criteria to be enrolled in this study: 1. Subjects voluntarily join this study, sign the informed consent form, have good compliance, and cooperation with the follow-up visit 2. Age≥ 18 years old (calculated on the day of signing informed consent) 3. Patients diagnosed with cervical cancer by pathology or histology, including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell neuroendocrine carcinoma, and have measurable lesions 4. Including the following locally advanced patients patients who are to be treated with concurrent chemoradiotherapy, ,with FIGO stage IIIC-IVA 5. ECOG score of 0-2 points 6. Expected survival time > 3 months 7. Tolerated with this study protocol and good organ function, please refer to the following: a) Neutrophil count ≥ 1500/μL b) White blood cell count ≥ 3000/mm3 c) Platelet ≥ 100,000/μL d) Hemoglobin ≥ 10g/dL e) Serum creatinine ≤1.5 times the upper limit of normal value, or creatinine clearance ≥ 60mL/min (calculated according to the Cockcroft-Gault formula) f) Total bilirubin ≤ 1.5 times the upper limit of normal value or direct bilirubin ≤ 1.0 times the upper limit of normal value g) AST and ALT ≤ 2.5 times the upper limit of normal value, and ≤5 times the upper limit of normal value must be in the presence of liver metastases h) Serum calcium≤ 2.5 times the upper limit of normal value i) Urine protein < 1000mg (24-hour urine collection) 8. Females of childbearing age who have a negative pregnancy test result at the time of enrollment and promise to take adequate and effective contraceptive measures or abstinence from the beginning of the study to the end of the study, and within 3 months after the last administration of the study drug can be enrolled in this study.

排除标准：

具有以下任何一项的患者不能入组本研究： 1. 妊娠期、哺乳期或计划在研究期间妊娠的女性受试者 2. 患有抗血管生成药物禁忌症患者 3. 既往接受过盆腔外照射放疗（包括经阴道近距离照射放疗） 4. 在过去的28天内进行大手术或开放性活检 5. 既往接受过全身化疗 6．预计生存期<3个月 7. 合并疾病/病史: a）入组前3个月内出现临床显著的咯血（每日咯血大于50ml）；或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，或患有脉管等 b）入组前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 c）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, 或服药时血压>160/90毫米汞柱） d）随机前6个月内，出现以下情况：过去12个月内心肌梗死、严重/不稳定型心绞痛、NYHA 3-4级心功能不全、需要药物治疗的室上性或室性心律失常以及症状性充血性心力衰竭 e）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） f）肾功能不全：尿常规提示尿蛋白≥++，或证实24小时尿蛋白量≥1.0g g）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 h）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 i）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；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入组）；给药前1年内有活动性结核感染证据 j）进入研究前3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 k）随机前28天之内进行过大手术（因诊断需要进行的组织活检和经外周静脉穿刺置入中心静脉导管操作[PICC]是允许的） l）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 m）周围神经病变≥2级者；活动性的脑转移、癌性脑膜炎、脊髓压迫患者，或筛选时影像学CT 或 MRI 检查发现脑或软脑膜的疾病（入组前14天已完成治疗且症状稳定的脑转移患者可以入组，但需经颅脑 MRI、CT或静脉造影评价确认为无脑出血症状） n）具有明显影响口服药物吸收的因素，如无法吞咽、慢性腹泻、存在具有显著临床意义的肠梗阻 o）具有动脉瘤、脑血管意外或动静脉畸形病史 p）严重的、无法愈合的伤口、溃疡或目前正在愈合的骨折 q）根据研究者的判断，有其他严重的危害患者安全或影响患者完成研究的伴随疾病 8．研究者认为可能干扰患者给予知情同意或合作参与研究或干扰研究者解释结果的任何其他医疗状况，包括精神疾病或药物滥用 9．无法完成研究或者随访，依从性差的患者 10．目前或近期（入组前4周内）或计划参加其他药物临床研究的患者

Exclusion criteria：

Patients with any of the following cannot be enrolled in this study: 1. Female subjects who are pregnant, lactating, or planning to become pregnant during the study 2. Patients with contraindications to anti-angiogenic drugs 3. Previous pelvic external beam radiation therapy (including transvaginal brachytherapy) 4. Major surgery or open biopsy within the past 28 days 5. Previous systemic chemotherapy 6. Estimated survival < 3 months 7. Comorbid Illness/History: a) Clinically significant hemoptysis (more than 50ml per day) within 3 months prior to enrollment; or significant clinically significant bleeding symptoms or with clear bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal occult blood (++) and above at baseline, or vascular, etc b) Arteriovenous thrombosis events that occurred within 6 months prior to enrollment, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis (except for those with venous thrombosis caused by intravenous catheterization in the early stage of chemotherapy and judged to have been cured by the investigator) and pulmonary embolism c) Hypertension that is not well controlled with antihypertensive medication (systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg, or blood pressure >160/90 mm Hg while taking medication) d) Within 6 months prior to randomization, the following conditions have occurred: myocardial infarction within the past 12 months, severe/unstable angina, NYHA grade 3-4 cardiac insufficiency, supraventricular or ventricular arrhythmias requiring medication, and symptomatic congestive heart failure e) Interstitial lung disease, non-infectious pneumonia or uncontrollable systemic diseases (e.g. diabetes, pulmonary fibrosis and acute pneumonia, etc.) f) Renal insufficiency: urine routine shows urine protein ≥++, or confirmed 24-hour urine protein volume ≥ 1.0g g) History of live attenuated vaccination within 28 days prior to the first study administration or expected live attenuated vaccination during the study period h) Human immunodeficiency virus (HIV) infection 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 lower limit of detection of the analytical method) or co-infection with hepatitis B and C i) Severe infection within 4 weeks prior to the first dose, including but not limited to bacteremia requiring hospitalization, severe pneumonia, etc.; Active infection of CTCAE≥2 grade 2 requiring treatment with systemic antibiotics within 2 weeks prior to the first dose, or unexplained fever >38.5°C during the screening period/before the first dose (as judged by the investigator, fever due to tumor causes can be enrolled); Evidence of active tuberculosis infection within 1 year prior to dosing j) Diagnosis of any other malignancy within 3 years prior to study entry, with the exception of adequately treated basal cell carcinoma or squamous cell skin cancer or carcinoma in situ of the cervix k) Major surgery within 28 days prior to randomization (tissue biopsy and peripherally venous catheter placement [PICC] required for diagnosis are permitted) l) Subjects who have received or are preparing to undergo allogeneic bone marrow transplantation or solid organ transplantation in the past m) Peripheral neuropathy ≥ grade 2; Patients with active brain metastases, carcinomatous meningitis, spinal cord compression, or diseases of the brain or leptomeninges detected by imaging CT or MRI at screening (patients with brain metastases who have completed treatment 14 days before enrollment and have stable symptoms can be enrolled, but they need to be confirmed by cranial MRI, CT, or venography evaluation as no symptoms of cerebral hemorrhage) n) Factors that significantly affect the absorption of oral drugs, such as inability to swallow, chronic diarrhea, and the presence of clinically significant intestinal obstruction o) Have a history of aneurysm, cerebrovascular accident, or arteriovenous malformation p) Severe, non-healing wounds, ulcers, or fractures that are currently healing q) According to the judgment of the investigator, there are other concomitant diseases that seriously endanger the safety of the patient or affect the completion of the study 8. Any other medical condition, including psychiatric illness or substance abuse, that, in the opinion of the investigator, may interfere with the patient's giving informed consent or cooperative participation in the study or with the investigator's interpretation of the results 9. Patients who are unable to complete the study or follow-up and have poor compliance 10. Patients who are currently or recently (within 4 weeks prior to enrollment) or plan to participate in other drug clinical studies

研究实施时间：

Study execute time：

从 From 2024-09-01 00:00:00至 To 2027-09-01 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2024-09-11 00:00:00 至 To 2027-03-01 00:00:00

干预措施：

Interventions：

组别：

试验组

样本量：

 30

Group：

treatment group

Sample size：

干预措施：

安罗替尼+紫杉醇/顺铂诱导治疗两周期后接受安罗替尼+同步放化疗 序贯高剂量率腔内放疗序贯化疗巩固治疗

干预措施代码：

Intervention：

Subjects received two cycles of induction therapy with anlotinib + paclitaxel/cisplatin and then received anlotinib + concurrent chemoradiotherapy sequential high-dose rate intraluminal radiotherapy and sequential chemotherapy consolidation therapy

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 甘肃 

市(区县)：

 兰州市 

Country：

China

Province：

gansu

City：

lanzhou

单位(医院)：

 甘肃省妇幼保健院/甘肃省中心医院 

单位级别：

 三甲 

Institution
hospital：

Gansu Provincial Maternal and Child Health Care Hospital/Gansu Provincial Central 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：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

肿瘤标志物的完全缓解率（CA199、SCCA均降至正常范围患者比例）

指标类型：

次要指标

Outcome：

complete response rate of tumor biomarkers(The proportion of patients with CA199 and SCCA decreased to normal range)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

12个月无复发生存期率

指标类型：

次要指标

Outcome：

12-month recurrence-free survival 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：

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：

反应持续时间

指标类型：

次要指标

Outcome：

Duration Of Response

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：

安全性

指标类型：

次要指标

Outcome：

Safety

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：

无

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 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）：

非随机

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

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：

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

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：

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, CRF

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2024-09-11 18:03:03