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：	ChiCTR2100044915
最近更新日期： Date of Last Refreshed on：	2021-10-30 23:30:20
注册时间： Date of Registration：	2021-03-31 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	一项开放、单臂的I期临床研究：评价SC0191片在晚期恶性实体瘤患者中的安全性、耐受性、药代动力学特征和药效动力学特征，并初步探索SC0191片的抗肿瘤活性
Public title：	An open-label, single-arm phase I clinical study: to evaluate the safety, tolerability, pharmacokinetic characteristics and pharmacodynamic characteristics of SC0191 tablets in patients with advanced malignant solid tumor, and to preliminarily explore the anti-tumor activity of SC0191 tablets
注册题目简写：
English Acronym：
研究课题的正式科学名称：	一项开放、单臂的I期临床研究：评价SC0191片在晚期恶性实体瘤患者中的安全性、耐受性、药代动力学特征和药效动力学特征，并初步探索SC0191片的抗肿瘤活性
Scientific title：	An open-label, single-arm phase I clinical study: to evaluate the safety, tolerability, pharmacokinetic characteristics and pharmacodynamic characteristics of SC0191 tablets in patients with advanced malignant solid tumor, and to preliminarily explore the anti-tumor activity of SC0191 tablets
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：	王波涛	研究负责人：	张力
Applicant：	Wang Botao	Study leader：	Zhang Li
申请注册联系人电话： Applicant telephone：	+86 18914172605	研究负责人电话： Study leader's telephone：	+86 13902282893
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：	wangbotao@sagacitypharma.com	研究负责人电子邮件： Study leader's E-mail：	zhangli@sysucc.org.cn
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：	上海市闵行区申长路988弄虹桥万科中心T1办公楼301B室	研究负责人通讯地址：	广州市越秀区东风东路651号
Applicant address：	301B Room, T1 Office, Hongqiao Vanke Center, Lane 988, Shenchang Road, Minhang District, Shanghai	Study leader's address：	651 Dongfeng Road East, Yuexiu District, Guanzhou
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：	石家庄智康弘仁新药开发有限公司
Applicant's institution：	Shijiazhuang Sagacity New Drug Development Company, Ltd.
研究负责人所在单位：	中山大学肿瘤防治中心
Affiliation of the Leader：	Cancer Center of Sun Yat-Sen University

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：	A2021-011-01	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：	中山大学肿瘤防治中心伦理委员会
Name of the ethic committee：	Cancer Center of Sun Yat-Sen University Ethics Committee
伦理委员会批准日期： Date of approved by ethic committee：	2021-02-03 00:00:00
伦理委员会联系人：	潘旭芝
Contact Name of the ethic committee：	Pan Xuzhi
伦理委员会联系地址：	广州市越秀区东风东路651号
Contact Address of the ethic committee：	651 Dongfeng Road East, Yuexiu District, Guanzhou
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：

中山大学肿瘤防治中心

Primary sponsor：

Sun Yat-Sen University Cancer Center

研究实施负责（组长）单位地址：

广州市东风东路651号

Primary sponsor's address：

651 Dongfeng Road East, Yuexiu District, Guanzhou

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	河北	市(区县)：	石家庄
Country：	China	Province：	Hebei	City：	Shijiazhuang
单位(医院)：	石家庄智康弘仁新药开发有限公司	具体地址：	高新区长江大道315号创新大厦16楼
Institution hospital：	Shijiazhuang Sagacity New Drug Development Co., Ltd	Address：	Floor 16, Innovation Buliding, 315 Changjiang Road, New and High-Tech District

经费或物资来源：

石家庄智康弘仁新药开发有限公司

Source(s) of funding：

Shijiazhuang Sagacity New Drug Development Company, Ltd.

研究疾病：

晚期实体瘤

Target disease：

Advanced solid tumor

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：

I期临床试验

Study phase：

1

研究设计：

单臂

Study design：

Single arm

研究目的：

主要目的： 1.评估SC0191片单药在晚期恶性实体瘤患者中的安全性和耐受性； 2.评估SC0191片单药DLT发生情况； 3.确定SC0191片单药的II期临床推荐剂量（RP2D）。次要目的： 1.评估SC0191片单药在晚期恶性实体瘤患者中的药代动力学（PK）特征； 2.评估SC0191片单药在晚期恶性实体瘤患者中的初步抗肿瘤活性； 3.评估SC0191片单药在晚期恶性实体瘤患者中的药效动力学（PD）特征与安全和疗效关系（仅在剂量扩展阶段）。

Objectives of Study：

Primary Objectives: 1.To confirm the safety and tolerability of SC0191 tablets in patients with advanced malignant solid tumor; 2.The incidence of DLT with single-agent SC0191; 3.To identify the recommended phase II dose (RP2D) of single-agent SC0191 tablets. Secondary Objectives: 1.To identify the pharmacokinetic (PK) profile of SC0191 tablets in patients with advanced malignant solid tumor; 2.To confirm the preliminary antitumor activity of single-agent SC0191 tablets in patients with advanced malignant solid tumor; 3.To evaluate the relationship between pharmacodynamics (PD) characteristics and safety and efficacy of single-agent SC0191 tablet in patients with advanced malignant solid tumors (only during the dose expansion stage).

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

Inclusion criteria (all the following criteria must be met):
1.For the dose escalating stag, histological or cytological diagnosis of advanced/metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available;
2.For the dose expansion stage, histological or cytological diagnosis of advanced/metastatic solid tumor that has progressed during or after standard treatment, and screened for defects of TP53, H3K36me3, or other DDR-associated genes;
3.Patients have at least one measurable lesion according to RECIST1.1 (in dose escalating stage, subjects have no measurable lesions but have evaluable lesions at the discretion of the treating physician are also allowed);
4.Subjects participate in the study voluntarily and have signed informed consent form;
5.Age >= 18 years old, <= 70 years old, male or female;
6.ECOG score of 0 to 2;
7.Life expectancy >= 3 months;
8.Patients must have normal organ and laboratory results as defined below:
Absolute Neutrophils Count >= 1.5 x 10^9/L;
Platelets >= 100 x 10^9/L;
Hemoglobin >= 90g/L, no blood transfusion or hematopoietic stimulating factor therapy received within 14 days;
Adequate Liver function as defined by: total serum bilirubin <= 1.5x upper normal limit (ULN). ALT and AST<=2.5xULN, no liver metastasis; AST and ALT<=5xULN if there is liver involvement secondary to tumor;
International Normalized Ratio <= 1.5;
Serum creatinine <=1.5 mg/dL or Estimated creatinine clearance >50 mL/min;
Fasting blood glucose <=140 mg/dL (7.8 mmol/L);
Lipase <= 1.5 x ULN;
If urine protein is >= 2+, the 24-hour urine protein excretion must be < 3.5g/24h;
9.Women of childbearing potential must have a negative serume pregnancy test within 7 days prior to the first dose and agree to use adequate contraception prior to study entry and for at least 3 months (or at least 90 days) after the last dose.Male subjects must consent to adequate contraception prior to study entry and for at least 3 months (or at least 90 days) after the last dose.

排除标准：

排除标准（只要满足一条标准即排除）：
1.首次给药前3周内接受过化疗、放疗、免疫治疗、内分泌治疗等抗肿瘤治疗。首次给药前6周内接受过亚硝基脲类或丝裂霉素C治疗。在首次给药前5个半衰期或14天内（视哪个更短）使用过小分子靶向药物，也应该排除；
2.首次使用试验药物前3周内接受过其它未上市的临床试验药物或治疗；
3.首次使用试验药物前3周内接受过主要脏器外科手术（不包括穿刺活检）或出现过显著外伤，或需要在试验期间择期手术；
4.首次使用试验药物前2周内接受过中药抗肿瘤治疗；
5.在剂量爬坡阶段，既往接受过WEE1抑制剂治疗；在剂量扩展阶段，既往接受过WEE1抑制剂或其它DDR相关抑制剂（如：PARP抑制剂）治疗；
6.既往抗肿瘤治疗的不良反应尚未恢复到 NCI CTCAE5.0等级评价<=1级（脱发、色素沉着、神经毒性等恢复到2级及以下，研究者判断无安全风险的毒性除外）；
7.符合以下情况的中枢神经系统转移患者：
(1)需要接受局部治疗（手术、放疗或其他）（脑转移无症状，研究者认为不需要局部治疗可以入组）；
(2)入组前正在服用类固醇激素>10mg泼尼松（或等效药物）；
(3)末次局部治疗后CNS转移不稳定或入组前稳定时间小于28天。
8.存在需要治疗的活动性感染；
9.符合研究中心活动性乙型肝炎感染标准（HBV DNA大于1000拷贝或200IU）或人类免疫缺陷病毒（HIV）抗体阳性或丙肝HCV抗体阳性（梅毒非活动性可以入组）。
10.心脏功能和疾病符合下述情况之一：
-筛选期在研究中心进行3次12导联心电图（ECG）测量，根据中心采用仪器的QTc公式计算三次平均值，QTc > 470毫秒；
-完全性左束支传导阻滞，II度及以上房室传导阻滞，快速型室性心动过速（包括频发室性早搏），尖端扭转型心律失常；
-任何增加QTc间期延长的风险因素，例如不可纠正的低钾血症、遗传性长QT综合征，服用延长QTc间期的药物（主要是Ia、Ic、III类抗心律失常药物）；
-美国纽约心脏病学会（NYHA）分级>=3级的充血性心力衰竭；
11.活动性消化系统疾病，或接受过重大消化道手术，或患有吸收不良综合症，或其他可能损害SC0191片吸收的情况（如溃疡性病变、不可控制的恶心、呕吐、腹泻、吸收障碍综合征和小肠切除术）；
12.既往间质性肺疾病史、药物引起的间质性肺疾病史、需要激素治疗的放射性肺炎；
13.既往胰腺炎史；
14.首次给药前14天内接受过CYP3A强抑制剂治疗（安普那韦、阿扎那韦、波普瑞韦、克拉霉素、考尼伐坦、地拉韦啶、地尔硫卓、红霉素、呋山那韦、茚地那韦、伊曲康唑、酮康唑、洛匹那韦、米贝拉地尔、咪康唑、奈法唑酮、奈非那韦、泊沙康唑、利托那韦、沙奎那韦、替拉瑞韦、泰利霉素、维拉帕米、伏立康唑等）或CYP3A强诱导剂治疗（卡马西平、非尔氨酯、奈韦拉平、苯巴比妥、苯妥英、扑米酮、利福布汀、利福平、利福喷丁等）；
15.哺乳期妇女；
16.研究者认为受试者存在其他严重的系统性疾病史、或其他原因而不适合参加本临床研究。

Exclusion criteria：

Exclusion criteria (as long as one criterion is met):
1.Subjects received chemotherapy, radiotherapy, immunotherapy, endocrine therapy and other anti-tumor therapies within 3 weeks before the first administration, 6 weeks for Nitrosolurea or mitomycin C; five half-lives or 14 day for small molecule targeting agents(whichever is shorter), should also be excluded.);
2.Received another unmarketed investigational drug or treatment within 3 weeks prior to initial use of the investigational drug;
3.Had major organ surgery (excluding needle biopsy) or significant trauma within 3 weeks prior to the first use of the investigational drug, or requires elective surgery during the study period;
4.Received traditional Chinese medicine with anti-tumor effect within 2 weeks before the first use of the drug;
5.Received WEE1 inhibitor treatment before in the dose-escalating stage; Previous treatment with WEE1 inhibitors or other DDR-related inhibitors (e.g., PARP inhibitors) during the dose expansion phase;
6.The subject has not recovered to NCI CTCAE5.0 grade evaluation<= 1 (from toxicity due to all prior therapies except alopecia, pigmentation, neurotoxicity, etc.,recovered to <= Grade 2, and other non-clinically significant toxicities determined by the investigator);
7.Patients with central nervous system metastases:
(1) Require local treatment (surgery, radiotherapy, or other) (patients with asymptomatic brain metastases and the investigator considers local treatment not required can be included);
(2) Taking >10mg prednisone (or equivalent drug) per day before enrollment;
(3) Unstable CNS metastasis after the last local treatment or being stable less than 28 days before enrollment.
8.The presence of active infections requiring treatment;
9.Meeting the study center's criteria for active hepatitis B infection (HBV DNA>= 1000 copies or 200IU) or positive to human immunodeficiency virus (HIV) or hepatitis C antibody (inactive syphilis can be enrolled).
10.Heart function or disease meets one of the following conditions:
-During the screening period, three 12-lead electrocardiogram (ECG) measurements will be carried out in the research center. According to QTC formula by the instruments in the center, the average values of three results for QTc > 470 ms;
(1) Complete left bundle branch block, degree II or above atrioventricular block, rapid ventricular tachycardia (including frequent premature ventricular beats), torsades de pointes;
(2) Any risk factors that prolong QTC interval, such as uncorrected hypokalemia, hereditary long QT syndrome, taking drugs that prolong QTC interval (mainly class Ia, Ic and III antiarrhythmic agents);
(3) Congestive heart failure: New York Heart Association (NYHA) >= grade 3;
11.Active digestive disease, or had major gastrointestinal surgery, or malabsorption syndrome, or other conditions that may impair the absorption of SC0191 tablets (such as ulcerative lesions, uncontrollable nausea, vomiting, diarrhea, malabsorption syndrome, and enteroctomies);
12.History of interstitial lung disease or drug-induced interstitial lung disease, radiation pneumonia requiring hormone therapy;
13.History of pancreatitis;
14.Subjects who have received a strong CYP3A inhibitor (Amprenavir, Atazanavir, Boceprevir, Clarithromycin, Conivaptan, Delavirdine, Diltiazem, Erythromycin, Fosamprenavir, Indinavir, Itraconazole, Ketoconazole, Lopinavir, Mibefradil, Miconazole, Nefazodone, Nelfinavir, Posaconazole, Ritonavir, Saquinavir, Telaprevir, Telithromycin, Verapamil, voriconazole,etc.) or a strong CYP3A inducer treatment (Carbamazepine, Felbamate, Nevirapine, Phenobarbital, Phenytoin, Primidone, Rifabutin, Rifampin, Rifapentine,etc.) within 14 days prior to the first administration;
15.Lactating women;
16.Subjects who have other serious systemic disease or reasons make him/her not suitable to enroll in this clinical study.

研究实施时间：

Study execute time：

从 From 2021-04-01 00:00:00至 To 2024-09-30 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2021-04-01 00:00:00 至 To 2023-12-31 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	62
Group：	Experimental group	Sample size：	62
干预措施：	口服SC0191片	干预措施代码：
Intervention：	Oral SC0191 piece	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	广东	市(区县)：	广州
Country：	China	Province：	Guangdong	City：	Guangzhou
单位(医院)：	中山大学肿瘤防治中心	单位级别：	三级甲等
Institution hospital：	Cancer Hospital of Sun Yat-Sen	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	剂量限制性毒性（DLT）	指标类型：	主要指标
Outcome：	Dose limiting toxicity (DLT)	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	安全性终点	指标类型：	次要指标
Outcome：	Safety endpoints	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	疗效终点：ORR、PFS、DOR、DCR等；	指标类型：	次要指标
Outcome：	Efficay end point: ORR, PFS, DOR, DCR, etc.	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	药代动力学指标：AUC0-last，AUC(0-24h)，AUC (0-∞)，Cmax，tmax，t1/2，Vd, CL/F，Ctrough，蓄积比Rac等	指标类型：	次要指标
Outcome：	Pharmacokinetic indicators:AUC0-last, AUC(0-24h), AUC (0-∞), Cmax, tmax, t1/2, Vd, CL/F, Ctrough, Accumulate index Rac, etc.	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	药效动力学指标：γH2AX、P-CDK1/2、dNTP（仅剂量扩展阶段）。	指标类型：	次要指标
Outcome：	Pharmacodynamics index: γH2AX, P-CDK1/2, dNTP (only during the dose expansion stage)	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	其它	说明	使用后保存至药品上市5年后销毁
Fate of sample：	0thers	Note：	Destruction after market for 5 years

征募研究对象情况：

Recruiting status：

正在进行

Recruiting

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）：

单臂试验，不采用随机。

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

Single arm test, no randomization.

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法：	N/A
Blinding：	N/A

是否共享原始数据： IPD sharing	是Yes
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）：	收集的原始数据将以学术论文的形式共享及发表，预计在2025年1-3月份。
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	The collected raw data will be shared and published as academic papers, expected during January to March 2025.
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：	采用电子采集和管理系统(Electronic Data Capture, EDC)形式收集所需所有数据，并进行管理及保存。
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Collect，manage and save all required Data in the form of 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：	2021-03-31 07:38:40