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：	ChiCTR-TNRC-08000194
最近更新日期： Date of Last Refreshed on：	2015-05-08 16:35:04
注册时间： Date of Registration：	2008-01-01 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	盐酸埃克替尼片对多种不同肿瘤患者,特别是非小细胞肺癌患者的I期、ⅡA期临床研究
Public title：	Phase I/IIA study of Icotinib Hydrochloride Tablets in Various Cancer Patients, mainly in Advanced Non-Small Cell Lung Cancer Patients
注册题目简写：
English Acronym：
研究课题的正式科学名称：	在对多种不同肿瘤患者,特别是非小细胞肺癌患者中，口服盐酸埃克替尼片，就其安全性、耐受性、药代动力学以及有效性进行的一项开放、单中心、I期和ⅡA临床研究
Scientific title：	An open-lable, single-center, phase I/IIA study to assess safety, tolerance, pharmacokinetics and efficacy of oral dosing icotinib hydrochloride tablets in various cancer patients,mainly in NSCLC
研究课题代号(代码)： Study subject ID：	BD-IC-I02
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：	周建娅	研究负责人：	赵琼
Applicant：	Zhou Jianya	Study leader：	Zhao Qiong
申请注册联系人电话： Applicant telephone：	+86 0571 87236873	研究负责人电话： Study leader's telephone：	+86 0571 87236873
申请注册联系人传真： Applicant Fax：	+86 0571 87236525	研究负责人传真： Study leader's fax：	+86 0571 87236525
申请注册联系人电子邮件： Applicant E-mail：	zhoujianya@hotmail.com	研究负责人电子邮件： Study leader's E-mail：	doczq.2008@163.com
申请单位网址(自愿提供)： Applicant website(voluntary supply)：	http://www.zy91.com/	研究负责人网址(自愿提供)： Study leader's website(voluntary supply)：	http://www.zy91.com/
申请注册联系人通讯地址：	浙江省杭州市庆春路79号浙江大学医学院附属第一医院呼吸内科	研究负责人通讯地址：	浙江省杭州市庆春路79号浙江大学医学院附属第一医院呼吸内科
Applicant address：	No.79, Qingchun Road, Shangcheng District, Hangzhou City, Zhejiang Province, China	Study leader's address：	No.79, Qingchun Road, Shangcheng District, Hangzhou City, Zhejiang Province, China
申请注册联系人邮政编码： Applicant postcode：	310003	研究负责人邮政编码： Study leader's postcode：	310003
申请人所在单位：	浙江大学医学院附属第一医院
Applicant's institution：	The First Affiliated Hospital, College of Medicine, Zhejiang University
研究负责人所在单位：
Affiliation of the Leader：

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：	(2007)伦审(药)第(64)号	伦理委员会批件附件： Approved file of Ethical Committee：
批准本研究的伦理委员会名称：	浙江大学医学院附属第一医院伦理委员会
Name of the ethic committee：	Ethic Committee of The First Affiliated Hospital, College of Medicine, Zhejiang University
伦理委员会批准日期： Date of approved by ethic committee：	2007-11-29 00:00:00
伦理委员会联系人：
Contact Name of the ethic committee：
伦理委员会联系地址：
Contact Address of the ethic committee：
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：

浙江大学医学院附属第一医院

Primary sponsor：

The First Affiliated Hospital, College of Medicine, Zhejiang University

研究实施负责（组长）单位地址：

浙江省杭州市庆春路79号

Primary sponsor's address：

No.79, Qingchun Road, Shangcheng District, Hangzhou City, Zhejiang Province, China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	-	省(直辖市)：	-	市(区县)：
Country：	-	Province：	-	City：
单位(医院)：	浙江贝达药业有限公司	具体地址：	杭州余杭经济开发区红丰路589号
Institution hospital：	Zhejiang Beta Pharma Inc.	Address：	No.589 Hongfeng Road, YuHang Economic Development Zone, Hangzhou, China

经费或物资来源：

浙江贝达药业有限公司

Source(s) of funding：

Zhejiang Beta Pharma Inc.

研究疾病：

非小细胞性肺癌

Target disease：

various cancer patients, mainly in advanced non-small cell lung cancer patients

研究疾病代码：

Target disease code：

研究类型：

观察性研究

Study type：

Observational study

研究所处阶段：

I期+II期

Study phase：

1-2

研究设计：

非随机对照试验

Study design：

Non randomized control

研究目的：

1.多种不同肿瘤患者,特别是非小细胞肺癌患者口服盐酸埃克替尼每天三次（TID）75mg、100mg、125mg、150mg、200mg、250mg，连续28天，评估它的安全性及耐受性；2. 评估稳态下盐酸埃克替尼的药代动力学参数；3.对用药剂量组和服用方法进行优化选择；4.在完成剂量递增并确定有效且安全的剂量后，扩大相应剂量组非小细胞肺癌的观察例数，进一步考察其后续治疗的安全性和疗效；5. 观察埃克替尼治疗非小细胞肺癌患者的无进展生存期（PFS）；6. 观察埃克替尼治疗非小细胞肺癌患者的的总生存期（OS）；7. 观察埃克替尼治疗非小细胞肺癌患者的的总体客观肿瘤缓解率（ORR）；8. 观察埃克替尼治疗非小细胞肺癌患者的的疾病控制率（DCR）；9. 观察埃克替尼治疗非小细胞肺癌患者的的疾病进展时间（TTP）；10.观察埃克替尼治疗非小细胞肺癌患者肺癌症状和健康相关的生活质量（HRQoL）；11.观察埃克替尼治疗非小细胞肺癌患者安全性

Objectives of Study：

1. The phase I study is to assess safety, tolerance of different doses (75mg, 100mg, 125mg, 150mg, 200mg, 250mg TID) of Icotinib Hydrochloride Tablets in various cancer patients, mainly in advanced non-small cell lung cancer patients and to assess pharmacokinetical parameters of steady state of icotinib in different doses; 2. The phase IIA study is to assess the anti-tumor effect and safety of Icotinib Hydrochloride Tablets in various cancer patients, mainly in advanced non-small cell lung cancer patients.

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. The patients with advanced solid tumors (including non-small cell lung cancer, pancreatic cancer, liver cancer, colorectal cancer, head and neck cancer, etc.) who are confirmed by histological or cytological diagnosis, previously treated at least one chemotherapy regimen (other than EGFR). The diseases relapse, ineffective, lack of effective conventional treatment or in stable stage;
2. Received cytotoxic chemotherapy drugs. And the end of chemotherapy treatment is at least four weeks from this registration to participate in this test. The subject must have recovered from any previous chemotherapy toxicity. The treatment must stop for more than three months, if it includes docetaxel or lung radiotherapy;
3. Patients with at least one measurable lesion meeting RECIST: ?At least one measurable lesion. Histology and/or cytology diagnosis will be necessary if patients with only one lesion. ?Lesions can be accurately measured in by the following methods: CT-scan of chest or abdomen or Magnetic resonance imaging (MRI), the 1 dimension as >=20 mm with conventional techniques, or as >=10 mm with spiral computed tomography (CT) scan;
4. ECOG Performance Status of 0, 1; and behavior condition integration (PS)<=1;
5. Life expectancy of at least 12 weeks;
6. To be aged from 18 to 70;
7. Adequate organ function, meeting the following: 
(1) Bone marrow: Absolute neutrophil count (ANC) >=1.5*10^9/L, Platelet count >=90*10^9/L, Hemoglobin >=9 g/dL;
(2) Hepatic: bilirubin <=1.5 times the upper limit of normal, ALT and AST <=3.0 * upper limit of normal (<=5 * upper limit of normal are acceptable if the liver has tumor involvement);
(3) Renal: endogeny CCR>=60mL/min based on the standard Cockcroft-Gault formula or Serum Creatinine <=1.5 times the upper limit of normal;
(4) No malabsorption or other disease which will affect the drug absorption.
8. Female: Women with childbearing potential must have a negative pregnancy test performed within 72 hours prior to treatment, or must use an approved contraceptive method during and for 3 months after the study; must have a negative serum or urine pregnancy test, and must not be breast-feeding';
9. Male: Must be surgically sterile or compliant with a contraceptive regimen during and for 3 months after the treatment;
10. Patients compliance and geographic proximity that allow adequate follow-up;
11. Ability to understand and the willingness to sign a written informed consent;
12. A signed informed consent must be obtained prior to performing any study specific procedures.

排除标准：

1. 在试验中使用过HER/EGFR抑制剂或其它靶分子药物（小分子药或单克隆抗体治疗），包括恩度、Avastin、Iressa、Tarceva、Sutent、Nexavar、Sprycel、Erbitux、Herceptin等进行过系统抗肿瘤治疗。2. 已知对埃克替尼或该产品的任一赋形剂严重过敏。3. 合并使用苯妥英钠、卡马西平、利福平、巴比妥或圣约翰草。4. 在试验用药第一天的前30天内使用未经批准的药品或其他试验用药。5. 患者各器官系统状况：新近诊断的中枢神经系统（CNS）转移，未接受明确的手术和/或放射治疗。对于既往诊断且治疗的CNS转移或脊髓压迫的患者，如果临床状态不稳定且需激素治疗。距之前的激素治疗间隔少于4周。既往患间质性肺病，药物诱导的间质性疾病，需要激素治疗的放射性肺炎或任何具临床证据的活动性间质性肺病。基线时CT扫描发现存在特发性肺纤维化。根据研究者判断，存在严重或不能控制的全身性疾病(如不稳定或不能代偿的呼吸、心脏，肝或肾脏疾病)的证据。任何不稳定的系统性疾病（包括活动性感染、四级高血压、不稳定心绞痛、充血性心力衰竭、肝肾或代谢性疾病）。在五年内患有任何其它恶性肿瘤（完全治愈的宫颈原位癌或基底细胞或鳞状上皮细胞皮肤癌除外）。任何显著的眼部异常，特别是严重的干眼综合征、干性角膜结膜炎、Sj?gren综合征、严重的暴露性角膜炎或其它可能增加角膜上皮损害的疾病。建议在试验期间不要使用角膜接触镜。是否继续佩戴角膜接触镜应与肿瘤科医师和眼科医师讨论决定。进入研究前存在临床可探测的（通过体检）第三间隙积液（例如腹水或胸腔积液），且无法通过引流或其他方法控制。既往有明确的神经或精神障碍史，包括癫痫或痴呆。6. 患者各器官病变的功能水平,绝对中性粒细胞计数（ANC）小于1.5×109 /L（1，500/mm3），血小板小于9×109 /L（100，000/mm3）或血红蛋白小于9g/dl。血清胆红素大于参考上限2倍。血清肌酐大于参考上限1.5倍或肌酐清除小于60ml/min。如果无肝转移，丙氨酸氨基转移酶（ALT）或者天门冬氨酸氨基转移酶（ATS）大于正常值上限的2.5倍或者肝转移时大于正常值上限的5倍。通过临床检查或动脉血氧分压（PaO2）＜60mmHg确定的肺功能不良。存在任何其他重要临床异常或实验室检查结果使得患者不适合参加研究的证据。进入研究前的6周内体重明显减轻（≥10％体重）。根据美国国立癌症研究所常见化疗毒副反应分级标准（NCI-CTC，第二版）有2级以上慢性毒性反应（不包括脱发）未痊愈者。7. 既往曾登记接受过本研究的治疗，或从本研究中退组的患者均不能入组。8. 期望寿命不多于12周。9. 参与计划和管理研究（适用于贝达药业有限公司员工或在研究机构的人员）。10.同时接受其他任何抗肿瘤治疗。11.妊娠或哺乳期妇女。12.研究人员认为，受试者未必能完成本研究或未必能遵守本研究的要求（由于管理方面的原因或其它原因）。

Exclusion criteria：

1. Have received HER/EGFR inhibitor and other molecular target drugs (micromolecular drug or MoAb) in other study, including endostar, Avastin, Iressa, Tarceva, Sutent, Nexavar, Sprycel, Erbitux and Herceptin;
2. Have a known hypersensitivity to icotinib or any of the excipient of icotinib;
3. concurrent treatment with sodium phenytoin, carbamazepine, rifampin, barbital or Sant Jone grass;
4. Have received treatment within the last 30 days with other study drug or a drug that has not received regulatory approval for any indication at the time of study entry;
5. Organ or system status:
(1) Known brain metastasis diagnosed recently which have not received surgery or radiotherapy. Patients has been off corticosteroids for at least 4 weeks before start study therapy if have prior CNS metastases or oppressing spinal cord. requiring corticosteroids treatment for unstable status;
(2) Have interstitial lung disease; have drug-induced pneumonia; have radiation pneumonia which requires treat with corticosteroids, have active interstitial lung disease evident on clinical evaluation;
(3) Have pre-existing idiopathic pulmonary fibrosis as evidenced by CT scan at baseline;
(4) Any serious or uncontrollable disease concomitant systemic disorder (such as unstable respiratory disorders, cardiovascular, hepatic or kidney disorders.) judged by the investigator according to evidence;
(5) Any unstable systemic disorders(including active infection, hypertension grade IV, unstable angina pectoris, congestive heart failure, liver and kidney disorder or metabolism disease);
(6) No other malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or treated cerviccal cancer in situ or squamous Cell Carcinoma of the Skin;
(7) Any remarkable eye disorders, especially severe dry eye syndrome, dry kerato- conjunctivitis, Sj'gren syndrome, serious exposition keratitis or other disease that possibly cause damage to epithelia of cornea. Not using contact lens will be better during the study, and whether or not using contact lens will be decided after discussing with oncologist and oculist;
(8) Have clinically detectable (by physical exam) third-space fluid collections (for example, ascites or pleural effusions) that cannot be controlled by drainage or other procedures prior to study entry;
(9) History of nerve or psychiatric disorder, including epilepsy or dementia.
6. Inadequate organ function including the following: ?Absolute neutrophil (segmented and bands) count (ANC) <1.5 *10^9/L (1,500/mm3), platelets <9 *10^9/L (100,000/mm3), or hemoglobin <9 g/dL;
(1) Bilirubin>1.5*upper limit of normal (ULN);
(2) Creatinine>1.5*upper limit of normal (ULN) or calculated creatinine clearance (CrCl) <60 mL/min;
(3) Aspartate transaminase (AST) and alanine transaminase (ALT)>2.5*ULN if the liver has no tumor involvement, aspartate transaminase (AST) and alanine transaminase (ALT) >5*ULN if the liver has tumor involvement;
(4) Lung function disorder confirmed by clinical examination or PaO2<60mmHg;
(5) Have any other significant clinical or lab test abnormity which would comprise the patient's ability to complete the study;
(6) Significant weight loss (>=10%), over the previous 6 weeks before study entry;
(7) >grade 2 uncured chronic toxic response (except alopecia) according to NCI-CTC (National Cancer Institute Common Terminology Criteria version 2.0);
7. Have previously registration or withdrawn from this study;
8. Life expectancy no more than 12 weeks;
9. Participate the plan and management of research (refer to the employees of beta pharmaceutical limited company or study institution people);
10. Concurrent administration of any other antitumor therapy;
11. Pregnant or breast- feeding;
12. Inability to comply with protocol or study procedures in the opinion of the investigator(management or any other reasons).

研究实施时间：

Study execute time：

从 From 2007-11-01 00:00:00至 To 2009-12-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2007-12-01 00:00:00 至 To 2009-05-31 00:00:00

干预措施：

Interventions：

组别：	150mg	样本量：	10
Group：	150mg	Sample size：	10
干预措施：	口服盐酸埃克替尼每天三次（TID）,连续28天，评估它的安全性及耐受性，稳态下盐酸埃克替尼的药代动力学参数。28天后继续服用,直至病情进展或出现不能耐受的毒性，评估它的有效性。	干预措施代码：
Intervention：	Oral dosing icotinib tablets, Tid, in continuing 28 days, to assess the safety, tolerance and pharmacokinetics of icotinib. The drug was continued after 28days until documented progressive disease or intolerable toxicity to assess the efficacy of icotinib	Intervention code：

组别：	200mg	样本量：	3
Group：	200mg	Sample size：	3
干预措施：	口服盐酸埃克替尼每天三次（TID）,连续28天，评估它的安全性及耐受性，稳态下盐酸埃克替尼的药代动力学参数。28天后继续服用，直至病情进展或出现不能耐受的毒性，评估它的有效性。	干预措施代码：
Intervention：	Oral dosing icotinib tablets, Tid, in continuing 28 days, to assess the safety, tolerance and pharmacokinetics of icotinib. The drug was continued after 28days until documented progressive disease or intolerable toxicity to assess the efficacy of icotinib	Intervention code：

组别：	75mg	样本量：	7
Group：	75mg	Sample size：	7
干预措施：	口服盐酸埃克替尼每天三次（TID）,连续28天，评估它的安全性及耐受性，稳态下盐酸埃克替尼的药代动力学参数。28天后继续服用，直至病情进展或出现不能耐受的毒性，评估它的有效性。	干预措施代码：
Intervention：	Oral dosing icotinib tablets, Tid, in continuing 28 days, to assess the safety, tolerance and pharmacokinetics of icotinib. The drug was continued after 28days until documented progressive disease or intolerable toxicity to assess the efficacy of icotinib	Intervention code：

组别：	250mg	样本量：	3
Group：	250mg	Sample size：	3
干预措施：	口服盐酸埃克替尼每天三次（TID）,连续28天，评估它的安全性及耐受性，稳态下盐酸埃克替尼的药代动力学参数。28天后继续服用，直至病情进展或出现不能耐受的毒性，评估它的有效性。	干预措施代码：
Intervention：	Oral dosing icotinib tablets, Tid, in continuing 28 days, to assess the safety, tolerance and pharmacokinetics of icotinib. The drug was continued after 28days until documented progressive disease or intolerable toxicity to assess the efficacy of icotinib	Intervention code：

组别：	125mg	样本量：	18
Group：	125mg	Sample size：	18
干预措施：	口服盐酸埃克替尼每天三次（TID），连续28天，评估它的安全性及耐受性（6例（行稳态下药代动力学参数研究）+扩大组14例）。28天后继续服用，直至病情进展或出现不能耐受的毒性，评估它的有效性。	干预措施代码：
Intervention：	Oral dosing icotinib tablets, Tid, in continuing 28 days, to assess the safety, tolerance and pharmacokinetics of icotinib. The drug was continued after 28days until documented progressive disease or intolerable toxicity to assess the efficacy of icotinib(Among them,14 patients were additional	Intervention code：

组别：	100mg	样本量：	30
Group：	100mg	Sample size：	30
干预措施：	口服盐酸埃克替尼每天三次（TID）,连续28天，评估它的安全性及耐受性（13例（行稳态下药代动力学参数研究）+扩大组17例）。28天后继续服用,直至病情进展或出现不能耐受的毒性，评估它的有效性。	干预措施代码：
Intervention：	Oral dosing icotinib tablets, Tid, in continuing 28 days, to assess the safety, tolerance and pharmacokinetics of icotinib. The drug was continued after 28days until documented progressive disease or intolerable toxicity to assess the efficacy of icotinib(Among them,17 patients were additional	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	浙江	市(区县)：	杭州
Country：	China	Province：	Zhejiang	City：	Hangzhou
单位(医院)：	浙江大学医学院附属第一医院	单位级别：	三级甲等
Institution hospital：	The First Affiliated Hospital, College of Medicine, Zhejiang University	Level of the institution：	Tertiary A hospital

测量指标：

Outcomes：

指标中文名：	受试者无进展生存期（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：	安全性	指标类型：	主要指标
Outcome：	Safety and tolerance	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	受试者QLQ评分及肿瘤疗效初步评估,	指标类型：	次要指标
Outcome：	Pharmacokinetics, QLQ rating and preliminary observation	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	受试者总生存期（OS）、总体客观肿瘤缓解率（ORR）、疾病控制率、疾病进展时间（TTP）和肺癌症状和健康相关的生活质量（HRQoL）	指标类型：	次要指标
Outcome：	Overall Survival, Objective Response Rate, Disease	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：

征募研究对象情况：

Recruiting status：

结束

/Completed

年龄范围：

Participant age：

最小 Min age	18	岁 years
最大 Max age	70	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）：

方便选择

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

Convenience selection

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）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

是否共享原始数据： IPD sharing
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）：	浙江大学医学院附属第一医院
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	The First Affiliated Hospital, College of Medicine, Zhejiang University
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：	杭州泰格医药有限公司
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Zhejiang Beta Pharma Inc.
数据与安全监察委员会： Data and Safety Monitoring Committee：
注册人： Name of Registration：	2009-07-27 00:00:00