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：	ChiCTR2400090522
最近更新日期： Date of Last Refreshed on：	2024-10-08 09:56:01
注册时间： Date of Registration：	2024-10-08 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	西达本胺联合安罗替尼±PD-1/PD-L1抑制剂治疗SWI/SNF复合物缺失性突变患者的前瞻性、开放标签、II期临床研究
Public title：	Prospective, open-label, phase II clinical study of the combination of Chidamide and Anlotinib ± PD-1/PD-L1 inhibitors in patients with SWI/SNF complex-deficient mutations
注册题目简写：
English Acronym：
研究课题的正式科学名称：	西达本胺联合安罗替尼±PD-1/PD-L1抑制剂治疗SWI/SNF复合物缺失性突变患者的前瞻性、开放标签、II期临床研究
Scientific title：	Prospective, open-label, phase II clinical study of the combination of Chidamide and Anlotinib ± PD-1/PD-L1 inhibitors in patients with SWI/SNF complex-deficient mutations
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：	刘雨桃	研究负责人：	刘雨桃
Applicant：	Yutao Liu	Study leader：	Yutao Liu
申请注册联系人电话： Applicant telephone：	+86 139 1190 1165	研究负责人电话： Study leader's telephone：	+86 139 1190 1165
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：	liuyutao@cicams.ac.cn	研究负责人电子邮件： Study leader's E-mail：	liuyutao@cicams.ac.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：	北京市朝阳区潘家园南里17号	研究负责人通讯地址：	北京市朝阳区潘家园南里17号
Applicant address：	No.17 Panjiayuan Nanli, Chaoyang District, Beijing P.R. China	Study leader's address：	No.17 Panjiayuan Nanli, Chaoyang District, Beijing P.R. 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：	中国医学科学院肿瘤医院
Applicant's institution：	Cancer Hospital Chinese Academy of Medical Sciences
研究负责人所在单位：	中国医学科学院肿瘤医院
Affiliation of the Leader：	Cancer Hospital Chinese Academy of Medical Sciences

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：	24/422-4702	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：	国家癌症中心/中国医学科学院北京协和医学院肿瘤医院伦理委员会
Name of the ethic committee：	Ethics Committee of National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
伦理委员会批准日期： Date of approved by ethic committee：	2024-08-14 00:00:00
伦理委员会联系人：	吴大维
Contact Name of the ethic committee：	Dawei Wu
伦理委员会联系地址：	北京市朝阳区潘家园南里17号
Contact Address of the ethic committee：	No.17 Panjiayuan Nanli, Chaoyang District, Beijing P.R. China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 10 8778 8495	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：

中国医学科学院肿瘤医院

Primary sponsor：

Cancer Hospital Chinese Academy of Medical Sciences

研究实施负责（组长）单位地址：

北京市朝阳区潘家园南里17号

Primary sponsor's address：

No.17 Panjiayuan Nanli, Chaoyang District, Beijing P.R. 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)：	北京	市(区县)：
Country：	China	Province：	Beijing	City：
单位(医院)：	中国医学科学院肿瘤医院	具体地址：	北京市朝阳区潘家园南里17号
Institution hospital：	Cancer Hospital Chinese Academy of Medical Sciences	Address：	No.17 Panjiayuan Nanli, Chaoyang District, Beijing P.R. China

经费或物资来源：

深圳微芯生物科技股份有限公司

Source(s) of funding：

Shenzhen Chipscreen Biosciences Co., Ltd.

研究疾病：

SWI/SNF复合物缺失性突变

Target disease：

Deletion Mutations in the SWI/SNF Complex

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：

非随机对照试验

Study design：

Non randomized control

研究目的：

评价西达本胺、安罗替尼联合或不联合PD-1/PD-L1抑制剂在SWI/SNF复合物缺失性突变患者中的疗效和安全性

Objectives of Study：

To evaluate the efficacy and safety of chidamide and anlotinib, with or without PD-1/PD-L1 inhibitors, in patients with deletion mutations in the SWI/SNF complex.

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) Aged 18 to 80, male or female.
(2) Patients with histologically or cytologically confirmed unresectable advanced or metastatic solid tumors.
(3) Patients with deletion mutations in SWI/SNF complex subunit genes (SMARCA1, SMARCA2, SMARCA4, SMARCB1, SMARCC2, SMARCC1, SMARCF1/ARID1A), or negative immunohistochemical results for related proteins (SNF2L, BRM, BRG1, BAF47, BAF170, BAF155, BAF250a).
(4) Standard treatment failure or intolerance to standard treatment.
(5) ECOG performance status of 0-2.
(6) Must have at least one measurable target lesion defined by RECIST v.1.1.
(7) Must have adequate organ and bone marrow function:
Blood tests: Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L; platelet count (PLT) ≥ 80 × 10^9/L; hemoglobin (HGB) ≥ 90 g/L.
Liver function: Serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); for patients without liver metastases, ALT and AST ≤ 3.0 × ULN; for those with liver metastases, ALT and AST ≤ 5.0 × ULN; serum albumin ≥ 25 g/L.
Kidney function: Serum creatinine (Cr) ≤ 1.5 × ULN.
Urinalysis showing urine protein < 2+; patients with baseline urinalysis showing urine protein ≥ 2+ should undergo 24-hour urine collection, and total 24-hour urine protein should be < 1 g.
Coagulation function: International normalized ratio (INR) ≤ 1.5 × ULN, and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
(8) Must voluntarily sign an informed consent form (ICF).
(9) Expected survival time of ≥ 3 months.
(10) Female subjects of childbearing age or male subjects with female partners of childbearing age must use effective contraception throughout the treatment period and for 6 months after treatment.

排除标准：

(1)先前使用过 HDAC 抑制剂或安罗替尼。 (2)在首次接受研究治疗前 28 天内接受过任何抗肿瘤治疗或研究药物和设备。 (3)在研究治疗的首次给药前 2 周内接受过放射治疗或在 6个月内接受过胸部放射>30Gy (4)尽管采取了标准治疗措施，但仍无法控制的（收缩压≥150mmHg或舒张压≥100mmHg）高血压患者。 (5)在研究治疗首次给药前 28 天内接受过全身免疫抑制药物。允许使用吸入或局部类固醇和生理剂量的全身糖皮质激素（每日≤10mg 泼尼松当量）。 (6)在研究治疗的首次给药前 28 天内接受过全身免疫刺激药物。 (7)在研究治疗的第一剂前 28 天内接种过活疫苗，或计划在研究期间接种。注意：注射用季节性流感疫苗通常是灭活流感疫苗，是允许的；COVID-19 疫苗也是允许的。 (8)在研究治疗的首次给药前 28 天内接受过重大手术。 (9)尚未从先前抗癌治疗导致的不良反应中恢复（≤ CTCAEV5.0定义的2级）。 (10)有症状且未经治疗的中枢神经系统转移。 (11)在研究治疗的首次给药前1个月内出现不可控的胸腔/腹腔/心包积液。 (12)无法控制的或者重大心脑血管疾病。 (13)首次服用研究治疗药物前2周内有咯血病史或2个月内有活动性出血病史；或正在服用抗凝剂的受试者，或筛选期间有明显的高危出血倾向的受试者。 (14)首次服用研究治疗药物前6个月内有严重血栓栓塞病史。 (15)疑似间质性肺病或肺纤维化或肺部炎症需要治疗；或在首次服用研究治疗前6个月内有使用口服或静脉注射类固醇治疗的肺病史。 (16)筛选期间出现明显胃肠道异常，可能影响药物的摄入、运输或吸收。 (17)筛选期间尿蛋白≥2+且尿蛋白定量≥1g/24h。 (18)需要静脉治疗的活动性感染；或研究治疗首次给药前28天内出现严重感染。 (19)已知的活动性肺结核，或正在接受抗结核治疗或在首次服用研究治疗前1年内曾经接受过抗结核治疗的受试者。 (20)已知患有急性或慢性活动性乙型肝炎（HBsAg 阳性且HBV DNA≥500 IU/mL 或≥103 拷贝数/mL）或急性或慢性活动性丙型肝炎（HCV 抗体阳性且HCV RNA阳性）。 (21)HIV 阳性或有艾滋病或其他严重传染病史。 (22)其他原发性恶性肿瘤病史，除外：入组前完全缓解至少2年的恶性肿瘤且在研究期间无需其他治疗；经充分治疗且无疾病复发证据的非黑色素瘤皮肤癌或恶性雀斑样痣；经充分治疗且无疾病复发证据的原位癌。 (23)筛选期间患有活动性自身免疫性疾病，并且在首次服用研究治疗前2年内接受过全身治疗。 (24)同种异体器官移植和同种异体造血干细胞移植的历史。 (25)对任何研究药物成分有禁忌。 (26)对研究药物或其任何赋形剂有过敏史。 (27)有酗酒或吸毒史。 (28)不愿意或无法遵守本协议所要求的程序。 (29)怀孕或哺乳期妇女。男性/女性不愿意或无法使用高效的避孕方法。 (30)研究者认为任何不适合参加试验的情况。

Exclusion criteria：

(1) Previously used HDAC inhibitors or anlotinib. (2) Received any anticancer treatments or investigational drugs and devices within 28 days prior to the first administration of the study treatment. (3) Received radiation therapy within 2 weeks prior to the first dose of the study treatment or received >30 Gy of chest radiation within the past 6 months. (4) Patients with uncontrolled hypertension (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg) despite standard treatment measures. (5) Received systemic immunosuppressive drugs within 28 days prior to the first administration of the study treatment. Inhaled or topical steroids and physiological doses of systemic corticosteroids (≤10 mg/day of prednisone equivalent) are allowed. (6) Received systemic immunostimulatory drugs within 28 days prior to the first administration of the study treatment. (7) Had vaccination with live vaccines within 28 days prior to the first dose of the study treatment or plan to be vaccinated during the study. Note: Injectable seasonal influenza vaccines are usually inactivated influenza vaccines and are permitted; COVID-19 vaccines are also allowed. (8) Underwent major surgery within 28 days prior to the first administration of the study treatment. (9) Has not recovered from adverse reactions caused by prior antitumor treatment (≤ Grade 2 as defined by CTCAE v5.0). (10) Symptomatic and untreated central nervous system metastasis. (11) Uncontrollable pleural/abdominal/pericardial effusion occurring within 1 month prior to the first administration of the study treatment. (12) Uncontrolled or significant cardiovascular or cerebrovascular diseases. (13) A history of hemoptysis within 2 weeks prior to the first administration of the study treatment or a history of active bleeding within 2 months; or subjects who are on anticoagulants, or have a significant high-risk of bleeding tendency during screening. (14) A history of serious thromboembolic events within 6 months prior to the first administration of the study treatment. (15) Suspected interstitial lung disease or pulmonary fibrosis, or pulmonary inflammation requiring treatment; or a history of pulmonary disease treated with oral or intravenous steroids within 6 months prior to the first administration of the study treatment. (16) Significant gastrointestinal abnormalities during screening that may affect the intake, transport, or absorption of the drug. (17) Urine protein ≥2+ and quantitative urine protein ≥1 g/24 h during screening. (18) Active infection requiring intravenous treatment; or severe infection occurring within 28 days prior to the first administration of the study treatment. (19) Known active tuberculosis, or currently undergoing anti-tuberculosis treatment, or having received anti-tuberculosis treatment within 1 year prior to the first administration of the study treatment. (20) Known to have acute or chronic active hepatitis B (HBsAg positive and HBV DNA ≥500 IU/mL or ≥10^3 copies/mL) or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA positive). (21) HIV positive or with a history of AIDS or other serious infectious diseases. (22) History of other primary malignant tumors, excluding malignant tumors that have been completely relieved for at least 2 years before enrollment and do not require any other treatment during the study period; Non melanoma skin cancer or malignant freckle nevi that have been adequately treated and have no evidence of disease recurrence; In situ cancer with sufficient treatment and no evidence of disease recurrence. (23) During the screening period, those who have active autoimmune diseases and have received systemic treatment within 2 years prior to the first use of the study treatment. (24) History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation. (25) There are contraindications to any research drug ingredients. (26) Have a history of allergies to the investigational drug or any of its excipients. (27) Have a history of alcohol or drug abuse. (28) Refusal or inability to comply with the procedures required by this agreement. (29) Pregnant or lactating women. Men/women are unwilling or unable to use efficient contraceptive methods. (30) The researcher considers any situation unsuitable for participating in the experiment.

研究实施时间：

Study execute time：

从 From 2024-10-08 00:00:00至 To 2026-10-07 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2024-10-08 00:00:00 至 To 2025-10-07 00:00:00

干预措施：

Interventions：

组别：	两药组	样本量：	29
Group：	Two-drug combination group	Sample size：	29
干预措施：	西达本胺+安罗替尼	干预措施代码：
Intervention：	Chidamide+ Anlotinib	Intervention code：

组别：	三药组	样本量：	28
Group：	Three-drug combination group	Sample size：	28
干预措施：	西达本胺+安罗替尼+PD-1/PD-L1抑制剂	干预措施代码：
Intervention：	Chidamide+ Anlotinib + PD-1/PD-L1 inhibitors	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	北京	市(区县)：
Country：	China	Province：	Beijing	City：
单位(医院)：	中国医学科学院肿瘤医院	单位级别：	三甲
Institution hospital：	Cancer Hospital Chinese Academy of Medical Sciences	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	12周PFS率	指标类型：	主要指标
Outcome：	12 week progression-free survival 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：	客观缓解率	指标类型：	次要指标
Outcome：	overall response 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：	无进展生存期	指标类型：	次要指标
Outcome：	progression-free 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：	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：	安全性	指标类型：	副作用指标
Outcome：	Safety	Type：	Adverse events
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：	肿瘤组织	组织：
Sample Name：	Tumor tissue	Tissue：
人体标本去向	使用后销毁	说明
Fate of sample：	Destruction after use	Note：

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：

正在进行

Recruiting

年龄范围：

Participant age：

最小 Min age	18	岁 years
最大 Max age	80	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）：

无

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

None

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

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)：	NA
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：	CRF
数据与安全监察委员会： Data and Safety Monitoring Committee：	暂未确定/Not yet
注册人： Name of Registration：	2024-10-08 09:55:53