今天是:2019-03-26 星期二

甲磺酸阿帕替尼用于III-IV期上皮性卵巢癌一线治疗后临床完全或部分缓解后的维持治疗的临床随机、开放、平行对照、多中心Ⅱ期临床试验
下载XML文档

注册号:

Registration number:

ChiCTR1900021912 

最近更新日期:

Date of Last Refreshed on:

2019-03-15 

注册时间:

Date of Registration:

2019-03-15 

注册号状态:

预注册  

Registration Status:

Prospective registration  

注册题目:

甲磺酸阿帕替尼用于III-IV期上皮性卵巢癌一线治疗后临床完全或部分缓解后的维持治疗的临床随机、开放、平行对照、多中心Ⅱ期临床试验 

Public title:

A randomized, open, parallel controlled, multicenter phase II trial of apatinib mesylate for maintenance therapy of stage III-IV epithelial ovarian cancer after first-line treatment with complete or partial remission 

注册题目简写:

 

English Acronym:

 

研究课题的正式科学名称:

甲磺酸阿帕替尼用于III-IV期上皮性卵巢癌一线治疗后临床完全或部分缓解后的维持治疗的临床随机、开放、平行对照、多中心Ⅱ期临床试验 

Scientific title:

A randomized, open, parallel controlled, multicenter phase II trial of apatinib mesylate for maintenance therapy of stage III-IV epithelial ovarian cancer after first-line treatment with complete or partial remission 

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:

唐洁 

研究负责人:

唐洁 

Applicant:

Jie Tang 

Study leader:

Jie Tang 

申请注册联系人电话:

Applicant telephone:

+86 15274836636 

研究负责人电话:

Study leader's telephone:

+86 15274836636 

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:

951593179@qq.com 

研究负责人电子邮件:

Study leader's E-mail:

951593179@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:

湖南省长沙市桐梓坡路283号 

研究负责人通讯地址:

湖南省长沙市桐梓坡路283号 

Applicant address:

283 Tongzipo Road, Yuelu District, Changsha, Hunan, China  

Study leader's address:

283 Tongzipo Road, Yuelu District, Changsha, Hunan, 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:

湖南省肿瘤医院 

Applicant's institution:

Hu'nan Previncial Cancer 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:

2019-69 

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:

湖南省肿瘤医院医学伦理委员会 

Name of the ethic committee:

Medical ethics committee of Hu'nan Previncial Cancer Hospital 

伦理委员会批准日期:

Date of approved by ethic committee:

2019-01-14 

伦理委员会联系人:

杨凤 

Contact Name of the ethic committee:

Feng Yang 

伦理委员会联系地址:

湖南省长沙市桐梓坡路283号 

Contact Address of the ethic committee:

283 Tongzipo Road, Yuelu District, Changsha, Hu'nan, China 

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:

湖南省肿瘤医院 

Primary sponsor:

Hu'nan Previncial Cancer Hospital 

研究实施负责(组长)单位地址:

湖南省长沙市桐梓坡路283号 

Primary sponsor's address:

283 Tongzipo Road, Yuelu District, Changsha, Hunan, 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):

湖南省

市(区县):

长沙

Country:

China

Province:

Hu'nan

City:

Changsha

单位(医院):

湖南省肿瘤医院

具体地址:

湖南省长沙市桐梓坡路283号

Institution
hospital:

Hu'nan Previncial Cancer Hospital

Address:

283 Tongzipo Road, Yuelu District

经费或物资来源:

江苏恒瑞医药股份有限公司 

Source(s) of funding:

Jiangsu Hengrui Medicine Co., Ltd. 

研究疾病:

上皮性卵巢癌 

Target disease:

epithelial ovarian 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:

研究目的:

观察和评价甲磺酸阿帕替尼片对III-IV期上皮性卵巢癌一线治疗后临床完全或部分缓解后的患者维持治疗的有效性和安全性。 

Objectives of Study:

To observe and evaluate the efficacy and safety of apatinib mesylate tablets in maintenance therapy for patients with stage III-IV epithelial ovarian cancer after first-line treatment with complete or partial clinical remission. 

药物成份或治疗方案详述:

 

Description for medicine or protocol of treatment in detail:

 

研究设计:

随机平行对照 

Study design:

Parallel 

纳入标准:

1. 年龄18岁~73岁。 2. 新诊断的、经组织学证实的高风险晚期(FIGO III-IV 期)上皮性卵巢癌、原发性腹膜癌和/或输卵管癌,且已经完成了一线含铂化疗(静脉的或腹膜内给药)的女性患者达到临床CR/PR。 3. III 期患者必须曾接受过一次最优减瘤术(前期或间隔减瘤术);IV 期研究患者必须进行过活检和/或前期或间隔减瘤术。 4. 随机分组之前已完成一线含铂(如卡铂或顺铂或其他铂)化疗(静脉或腹膜内给药)的患者: (1) 必须在完成本次化疗后,经研究者判断认为在治疗后影像检查显示出现临床完全缓解或部分缓解且无疾病进展的临床证据或 CA-125 水平升高。完成一线含铂化疗后,治疗后影像检查显示病情稳定的患者不符合研究入选资格。 (2) 整个研究方案中使用的“反应”是指经研究者判断认为根据治疗后影像检查判断认为患者出现了临床完全缓解或部分缓解。临床完全缓解定义为治疗后影像检查显示无 RECIST1.1版 可测量或非可测疾病的证据和 CA-125 水平正常。部分缓解定义为根据治疗后影像检查显示从化疗开始到结束肿瘤体积减少≥30%或无 RECIST1.1版可测量疾病的证据及 CA-125 水平未降低至正常范围内。 (3) 含铂化疗疗程至少包含6个治疗周期,至多9个治疗周期,但是如果由于铂治疗导致毒性反应而必须中止铂化疗,则患者必须至少已经接受了4个铂治疗周期。 (4) 患者必须在最后一次化疗给药后 8 周内随机分组(最后一次给药即为最后一次输注的当天)。 5. 治疗前 CA-125 的检测结果必须满足以下特定标准: (1) 若第一次检测值小于等于正常值上限(ULN),则患者可进行随机分组且无需进行第二次采样。 (2) 若第一次检测值大于 ULN,则必须在第一次检测至少7天后进行第二次评估。若患者第二次评估值比第一次评估值高出≥15%,则患者无资格入选。 6. 患者在研究治疗给药之前的 28 天内器官和骨髓功能必须正常,定义如下: (1) 28 天内未接受输血且血红蛋白 ≥ 10.0 g/dL; (2) 中性粒细胞绝对计数(ANC) ≥ 1.5 x 10^9/L; (3) 血小板计数≥ 100x10^9/L; (4) 总胆红素≤1.5 倍正常值上限(ULN); (5) 天门冬氨酸氨基转移酶(AST)(血清谷草转氨酶(SGOT))/丙氨酸氨基转移酶(ALT)(血清谷丙转氨酶(SGPT))≤ 2.5 倍 正常值上限,若存在肝转移,则应≤ 5 倍 ULN; (6) 血清肌酐≤ 1.5 倍 ULN。 7. 患者在研究治疗给药之前的30天内无活动性出血、溃疡、肠穿孔、肠梗阻及大手术。 8. 预计生存期超过3个月。 9. 绝经或具有生育能力的女性已证明未怀孕: 在研究治疗之前的 28 天内的尿液或血清妊娠试验呈阴性,并在第一天治疗之前证实。绝经后定义为: (1) 外源性激素治疗中断后闭经一年或以上; (2) 促黄体激素(LH)和促卵泡激素(FSH)水平在 50 岁以下妇女的绝经后范围内; (3) 放射线诱导卵巢切除术,末次月经在>1年前; (4) 化疗诱导的绝经,末次月经在>1年前; (5) 绝育手术(双侧卵巢切除术或子宫切除术)。 10. 在研究期间,患者愿意并能够遵从研究方案接受治疗、定期随访和检查。 

Inclusion criteria

1. Aged 18 to 73 years. 2. Women with newly diagnosed and histologically proven high-risk advanced (FIGO III-IV) epithelial ovarian cancer, primary peritoneal cancer and/or fallopian tube cancer who have completed first-line platinum-containing chemotherapy (intravenous or intraperitoneal administration) have achieved clinical CR/PR. 3. Phase III patients must have undergone an optimal tumour reduction (pre-or septal tumour reduction); phase IV patients must undergo biopsy and/or pre-or septal tumour reduction. 4. Patients who had completed first-line platinum-containing chemotherapy (such as carboplatin or cisplatin or other platinum) prior to randomization (intravenous or intraperitoneal administration): (1) After the completion of the chemotherapy, the researchers judged that after the treatment, imaging examination showed complete or partial clinical remission without disease progression or elevated CA-125 level. After completing the first-line platinum-containing chemotherapy, imaging examination after treatment showed that patients with stable condition did not qualify for the study. (2) The "response" used in the whole research program refers to the judgement of the researcher that the patient had complete or partial clinical remission according to the image examination after treatment. Clinical complete remission is defined as no evidence of measurable or non-measurable diseases in RECIST 1.1 and normal CA-125 levels after treatment. Partial remission is defined as the reduction of tumor volume by more than 30% or the absence of evidence of measurable disease in RECIST 1.1 from the beginning to the end of chemotherapy and the absence of CA-125 levels within the normal range according to imaging findings after treatment. (3) The platinum-containing chemotherapy course includes at least six treatment cycles and at most nine treatment cycles. However, if platinum-containing chemotherapy must be discontinued due to toxic reactions caused by platinum therapy, the patient must have received at least four platinum treatment cycles. (4) Patients must be randomly divided into groups within 8 weeks of the last chemotherapy (the last administration is the day of the last infusion). 5. The detection results of CA-125 before treatment must meet the following specific criteria: (1) If the first detection value is less than or equal to the upper limit of normal value (ULN), patients can be randomly grouped without the need for a second sampling. (2) If the first detection value is greater than ULN, a second evaluation must be made at least 7 days after the first detection. If the second evaluation value of patients is higher than or equal to 15% of the first evaluation value, the patients will not be eligible for admission. 6. Organ and bone marrow function must be normal within 28 days prior to the study of treatment, defined as follows: (1) No blood transfusion was received within 28 days and hemoglobin (> 10.0 g/dL); (2) Absolute neutrophil count (ANC) > 1.5 x 10^9/L; (3) Platelet count (> 100X10 ^ 9/L); (4) The upper limit of normal value (ULN) of total bilirubin < 1.5 times; (5) Aspartate aminotransferase (AST) (serum glutamic oxalate aminotransferase (SGOT) / alanine aminotransferase (ALT) (serum glutamic alanine aminotransferase (SGPT) = 2.5 times the upper limit of normal value, if there is liver metastasis, it should be less than 5 times ULN; (6) Serum creatinine < 1.5 times ULN. 7. No active bleeding, ulcer, intestinal perforation, intestinal obstruction and major surgery were performed within 30 days prior to the study. 8. The life expectancy is expected to exceed 3 months. 9. Menopausal or fertile women have proved not pregnant: urine or serum pregnancy tests within 28 days prior to treatment were negative and confirmed before the first day of treatment. Postmenopausal is defined as: (1) Amenorrhea after interruption of exogenous hormone therapy for one year or more; (2) The levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were within the postmenopausal range of women under 50 years old. (3) Radiation-induced ovariectomy, the last menstruation was more than one year ago; (4) Chemotherapy-induced menopause, the last menstruation was more than one year ago; (5) Sterilization (bilateral ovariectomy or hysterectomy). 10. During the study period, patients were willing and able to follow the research program for treatment, regular follow-up and examination. 

排除标准:

1. 患者治疗后影像检查显示病情稳定或疾病进展,或者一线化疗结束时有疾病进展的临床证据。 2. 对甲磺酸阿帕替尼任何成分过敏者。 3. 过去 5 年内出现过其他恶性肿瘤,以下情况除外:充分治疗的非黑色素瘤皮肤癌,有效治疗的宫颈原位癌,I 期导管原位癌(DCIS),I 期 1 级子宫内膜癌,或其他实体瘤包括有效治疗且无疾病证据达 5 年以上的淋巴瘤(未累及及骨髓)。有局部乳腺癌既往病史的患者可能有资格入选,前提是在登记入组研究前辅助化疗已结束 3 年以上,且患者无复发性或转移性疾病。 4. 24 小时内 2 个或 2 个以上时间点的静息心电图 QTc> 470 毫秒或有长 QT 综合征家族史。 5. 在研究治疗之前的 3 周内(或更长的时间,取决于所用药品特征)接受任何全身化疗或放疗(姑息原因除外)。 6. 此前癌症治疗造成持久性毒性(>2级不良事件通用术语标准(CTCAE)),脱发除外。 7. 骨髓增生异常综合征/急性髓细胞白血病患者。 8. 若在研究治疗开始之前 2 周内接受了大手术,则患者必须已经从大手术的影响中恢复。 9. 由于严重的、无法控制的医学疾病,非恶性全身性疾病或活动性、无法控制的感染导致患者具有较大的医学风险。实例包括但不限于不受控制的室性心律失常,近期(3 个月内)心肌梗死,不受控制的癫痫大发作,不稳定的脊髓压迫,上腔静脉综合征,由高分辨率计算机断层扫描(HRCT)显示的双肺广泛间质性疾病或任何导致无法签署知情同意的精神疾病。 10. 无法吞咽口服制剂和胃肠功能紊乱的患者,可能会干扰研究药物的吸收。 11. 哺乳期妇女。 12. 免疫功能低下的患者,例如,人类免疫缺陷病毒血清反应阳性的患者(HIV)。 13. 已知患者对阿帕替尼或其辅料有超敏反应。 14. 已知有活动性肝炎的患者(即乙型肝炎或丙型肝炎),如患者HBsAg + ,HBV DNA <1*104copies/ml(2000IU/ml)仍可进入研究,其具有血液或其他体液传播的感染风险。 15. 此前接受骨髓同种异体移植。 16. 在研究开始之前 120 天内接受过全血输血。 17. 药物不可控制的高血压、3-4级心功能不全(NYHA标准)、重度肝肾功能不全(4级)。 18. 研究者判断其他可能影响临床研究进行及研究结果判定的情况。 

Exclusion criteria:

1. Images of patients after treatment showed stable condition or disease progression, or clinical evidence of disease progression at the end of first-line chemotherapy. 2. Allergic to any component of Apatinib Mesylate. 3. Other malignant tumors have occurred in the past five years, except for adequately treated non-melanoma skin cancer, effectively treated cervical cancer in situ, stage I ductal carcinoma in situ (DCIS), stage I endometrial cancer, or other solid tumors, including lymphomas that have been effectively treated and have no evidence of disease for more than five years (not involving bone marrow). Patients with a history of local breast cancer may be eligible for inclusion, provided that adjuvant chemotherapy has been completed for more than three years before enrollment and that patients have no recurrent or metastatic diseases. 4. Resting electrocardiogram (ECG) QTc > 470 milliseconds or family history of long QT syndrome at 2 or more time points within 24 hours. 5. Accept any systemic chemotherapy or radiotherapy (except for palliative reasons) within three weeks (or longer, depending on the characteristics of the drug used) prior to the study. 6. Previous cancer treatment resulted in persistent toxicity (> CTCAE), excluding hair loss. 7. Patients with myelodysplastic syndrome/acute myeloid leukemia. 8. If a major operation is performed within two weeks before the start of the study, the patient must have recovered from the impact of the major operation. 9. Because of serious and uncontrollable medical diseases, patients with non-malignant systemic diseases or active and uncontrollable infections have greater medical risks. Examples include, but are not limited to, uncontrolled ventricular arrhythmias, recent (3-month) myocardial infarction, uncontrolled epileptic seizures, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial disease of the lungs as shown by high-resolution computed tomography (HRCT), or any psychiatric disorder that leads to the failure to sign informed consent. 10. Patients who are unable to swallow oral preparations and gastrointestinal dysfunction may interfere with the absorption of research drugs. 11. Lactating women. 12. Patients with low immune function, such as those with positive serum response to human immunodeficiency virus (HIV). 13. Patients are known to have hypersensitivity to apatinib or its excipients. 14. Patients with known active hepatitis (i.e. hepatitis B or C), such as patients with HBsAg +, HBV DNA < 1*104copies/ml (2000IU/ml), can still be studied, and they are at risk of infection transmitted by blood or other body fluids. 15. Previous bone marrow allotransplantation. 16. Full blood transfusions were received within 120 days before the start of the study. 17. Uncontrolled hypertension, grade 3-4 cardiac insufficiency (NYHA standard), and severe hepatorenal insufficiency (grade 4). 18. Researchers judge other situations that may affect the conduct of clinical research and the outcome of research. 

研究实施时间:

Study execute time:

From2019-04-01To 2021-01-31 

干预措施:

Interventions:

组别:

试验组

样本量:

62

Group:

Experimental Group

Sample size:

干预措施:

阿帕替尼(175mg,qd)口服

干预措施代码:

Intervention:

Apatinib (175 mg, qd) orally

Intervention code:

组别:

对照组

样本量:

62

Group:

Control Group

Sample size:

干预措施:

NA

干预措施代码:

Intervention:

NA

Intervention code:

研究实施地点:

Countries of recruitment and research settings:

国家:

中国 

省(直辖市):

湖南省 

市(区县):

长沙 

Country:

China 

Province:

Hunan 

City:

Changsha 

单位(医院):

湖南省肿瘤医院 

单位级别:

三级甲等 

Institution
hospital:

Hunan Cancer Hospital  

Level of the institution:

Tertiary A hospital 

国家:

中国 

省(直辖市):

湖南省 

市(区县):

怀化 

Country:

China 

Province:

Hunan 

City:

Huaihua 

单位(医院):

怀化市第一人民医院 

单位级别:

三级甲等 

Institution
hospital:

First people's Hospital of Huaihua  

Level of the institution:

Tertiary A hospital 

国家:

中国 

省(直辖市):

湖南省 

市(区县):

怀化 

Country:

China 

Province:

Hunan 

City:

Huaihua 

单位(医院):

怀化市第二人民医院 

单位级别:

三级甲等 

Institution
hospital:

Huaihua Second people's Hospital  

Level of the institution:

Tertiary A hospital 

国家:

中国 

省(直辖市):

湖南省 

市(区县):

娄底 

Country:

China 

Province:

Hunan 

City:

Loudi 

单位(医院):

娄底市中心医院 

单位级别:

三级甲等 

Institution
hospital:

The Central Hospital of Loudi  

Level of the institution:

Tertiary A hospital 

国家:

中国 

省(直辖市):

湖南省 

市(区县):

岳阳 

Country:

China 

Province:

Hunan 

City:

Yueyang 

单位(医院):

岳阳市第一人民医院 

单位级别:

三级甲等 

Institution
hospital:

The First People's Hospital of YueYang  

Level of the institution:

Tertiary A hospital 

国家:

中国 

省(直辖市):

湖南省 

市(区县):

邵阳 

Country:

China 

Province:

Hunan 

City:

Shaoyang 

单位(医院):

邵阳市中心医院 

单位级别:

三级甲等 

Institution
hospital:

The Central Hospital of Shaoyang  

Level of the institution:

Tertiary A hospital 

国家:

中国 

省(直辖市):

湖北省 

市(区县):

武汉 

Country:

China 

Province:

Hubei 

City:

Wuhan 

单位(医院):

湖北省肿瘤医院 

单位级别:

三级甲等 

Institution
hospital:

Hubei Cancer Hospital  

Level of the institution:

Tertiary A hospital 

国家:

中国 

省(直辖市):

广西壮族自治区 

市(区县):

南宁 

Country:

China 

Province:

Guangxi Guangxi Zhuang Autonomous Region 

City:

Nanning 

单位(医院):

广西省肿瘤医院 

单位级别:

三级甲等 

Institution
hospital:

The Affiliated Cancer Hospital of Guangxi Medical University  

Level of the institution:

Tertiary A hospital 

测量指标:

Outcomes:

指标中文名:

无进展生存期(PFS)

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(OS)

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:

生活质量评分QoL

指标类型:

次要指标 

Outcome:

Quality of life score QoL

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

探索性分子标志物

指标类型:

次要指标 

Outcome:

Exploratory molecular markers

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 years
最大 Max age 73 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):

受试者按照1:1随机分组,被分配至阿帕替尼组或者对照组。本试验采用中心化随机分组的方法,各家中心竞争入组。中心化随机分组程序将采用南京医科大学流行病与卫生统计学系提供的中心化随机分组系统,参加本试验的各试验中心研究人员在筛选出每一例合格受试者后,经该中心研究者确认后登录随机系统,填写筛选资料,获取药物编号信息,按药物编号发放相应的研究药物。

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

Subjects were randomly divided into 1:1 groups and assigned to the Apatinib group or the control group. In this study, a centralized randomized grouping method was used, and each center competed to be grouped. The centralized randomized grouping procedure will adopt the centralized randomized grouping system provid

盲法:

open

Blinding:

open

试验完成后的统计结果(上传文件):

Calculated Results after
the Study Completed(upload file):

原始数据公开时间:

The time of sharing IPD:

即时公开/Real time access

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):

国际知名的SCI妇科肿瘤杂志

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

Decent iternational gynecologic onclogic journal

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:

Electronic Data Capture, EDC

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

Electronic Data Capture, EDC

数据管理委员会:

Data Managemen Committee:

有/Yes

注册人:

Name of Registration:

 2019-03-15
返回列表