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：	ChiCTR2100043643
最近更新日期： Date of Last Refreshed on：	2025-02-26 09:34:35
注册时间： Date of Registration：	2021-02-24 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	新型溶瘤病毒联合安罗替尼治疗晚期肺癌、肝癌等恶性实体肿瘤的前瞻、开放、单臂对照临床研究
Public title：	Novel oncolytic virus combined with Anlotinib treatment in patients with advanced lung cancer, liver cancer and other malignant solid tumors: a prospective, open, single-arm, phase 2 trial
注册题目简写：
English Acronym：
研究课题的正式科学名称：	新型溶瘤病毒联合安罗替尼治疗晚期肺癌、肝癌等恶性实体肿瘤的前瞻、开放、单臂对照临床研究
Scientific title：	Novel oncolytic virus combined with Anlotinib treatment in patients with advanced lung cancer, liver cancer and other malignant solid tumors: a prospective, open, single-arm, phase 2 trial
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：	李春姗	研究负责人：	李春姗
Applicant：	Chunshan Li	Study leader：	Chunshan Li
申请注册联系人电话： Applicant telephone：	+86 18507810785	研究负责人电话： Study leader's telephone：	+86 18507810785
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：	pingting4746zhong@163.com	研究负责人电子邮件： Study leader's E-mail：	pingting4746zhong@163.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：	广西南宁仙葫经济开发区仙葫大道	研究负责人通讯地址：	广西南宁青秀区东葛路89-9号
Applicant address：	Xianhu Avenue, Xianhu Economic Development Zone, Nanning, Guangxi Zhuang Autonomous Region, China	Study leader's address：	89-9 Dongge Road, Qingxiu District, Nanni
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：	广西中医药大学第一附属医院
Applicant's institution：	The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine
研究负责人所在单位：	广西中医药大学第一附属医院
Affiliation of the Leader：	The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine

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：	2020-048-02	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：	广西中医药大学第一附属医院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee of the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine
伦理委员会批准日期： Date of approved by ethic committee：	2021-01-29 00:00:00
伦理委员会联系人：	黎老师
Contact Name of the ethic committee：	Mr. Li
伦理委员会联系地址：	广西南宁青秀区东葛路89-9号
Contact Address of the ethic committee：	89-9 Dongge Road, Qingxiu District, Nanning, Guangxi Zhuang Autonomous Region, China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 771-5323553	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：

广西中医药大学第一附属医院

Primary sponsor：

The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine

研究实施负责（组长）单位地址：

广西南宁青秀区东葛路89-9号

Primary sponsor's address：

89-9 Dongge Road, Qingxiu District, Nanning, Guangxi Zhuang Autonomous Region, 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)：	广西	市(区县)：
Country：	China	Province：	Guangxi Zhuang Autonomous Region	City：
单位(医院)：	广西中医药大学第一附属医院	具体地址：	仙葫经济开发区仙葫大道
Institution hospital：	The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine	Address：	Xianhu Avenue, Xianhu Economic Development Zone

经费或物资来源：

国家科技重大专项重大新药创新项目

Source(s) of funding：

Major new drug innovation projects of major national science and technology projects

研究疾病：

各种恶性肿瘤

Target disease：

Various malignant tumors

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-III期临床试验

Study phase：

2-3

研究设计：

单臂

Study design：

Single arm

研究目的：

观察新型溶瘤病毒及安罗替尼治疗晚期肺癌、肝癌等恶性实体肿瘤的安全性、耐受性和有效性。

Objectives of Study：

Observe the effectiveness, safety and tolerability of new oncolytic viruses and Anlotinib in the treatment of advanced lung cancer, liver cancer and other malignant solid tumors.

药物成份或治疗方案详述：

1）新型溶瘤病毒制剂： 1~3×10^7-10pfu/kg，静脉注射，或腹腔注射、瘤内注射，也可以同时注射，每周一次，连续用8-12周。 2）安罗替尼胶囊： 12mg po qd d1-14，q3w（医师指导下调整剂量：①第一次调整剂量：10mg，每日一次，连服2周，停药1周：②第二次调整剂量：8mg，每日一次，连服2周，停药药1周，如8mg剂量仍无法耐受，则停药）

Description for medicine or protocol of treatment in detail：

1.New oncolytic virus preparation: 1~3 x 10^7-10pfu/kg, intravenous injection, intraperitoneal injection, intratumor injection, or simultaneous injection, once a week, for continuous 8-12 weeks. 2.Anlotinib capsules: 12mg po qd d1-14, q3w (adjusted dose under the guidance of a physician: (1)The first adjusted dose: 10mg, once a day, for 2 weeks, stop for 1 week: (2)The second adjusted dose: 8mg, once a day. Take 2 weeks, stop the drug for 1 week, if the 8mg dose is still intolerable, stop the drug).

纳入标准：

肝癌的纳入标准
1）年龄在18至75岁，性别不限；
2）经组织/细胞学及影像学确诊的晚期肝细胞肝癌（不可手术或转移性）并缺乏标准治疗或不具备标准治疗条件的患者；
3）Child-pugh肝功能评级：A级、B级；
4）PET-CT检查至少一个可测量病灶（按RECIST1.1标准）；
5）入组前患者接受上一次抗肿瘤治疗后至少4周或大于5个半衰期；姑息性手术后1个月以上；
6）预期生存时间≥3月；
7）终末期肝病模型（MELD）评分＜9分；
8）能合作观察不良事件和疗效，试验开始至结束期间进行PET-CT检查；
9）无其他抗肿瘤伴随治疗（包括类固醇药物）；
10）ECOG评分≤2；
11）血清白蛋白≥30g/L，血清ALT≤190U/L，AST≤200 U/L，血清TBIL≤1.5×ULN，电解质正常或经过治疗后达到正常，蛋白尿=0~1+，血肌酐≤1.5×ULN；
12）血常规检查标准需符合：HB≥ 80g/L；ANC≥1.5×10^9/L；PLT ≥70×10^9/L；
13）患者自愿签署书面知情同意书。

肺癌的纳入标准
1）自愿参加本次临床试验，理解研究程序且已签署知情同意；
2）年龄：18~75 周岁的男性或女性患者；
3）病理学及影像学诊断为晚期肺癌患者；
4）按东部肿瘤合作组织（ECOG）标准，体能状态为0~2分；
5）预期生存期不少于3个月；
6）根据RECIST1.1版实体肿瘤疗效评价标准，患者至少有一处PET-CT可测量病灶，要求最长径≥10 mm（若为淋巴结，则要求短轴≥15 mm）（脑转移病灶不作为唯一可测量病灶）；
7）受试者必须具有适当的器官功能，入组前符合下列实验室检查结果：骨髓储备基本正常：中性粒细胞绝对计数≥1.5×10^9/L ，血小板≥100×10^9/L ，以及血红蛋白≥80g/L；肝脏功能基本正常：血清中白蛋白≥3.0 g/dL ；胆红素≤1.5 ×ULN，ALT 和AST ≤2.5 ×ULN，如有肝转移，则ALT 或AST≤5×ULN；肾功能正常：肌酐≤1.5 倍ULN 或24 小时肌酐清除率≥60 mL/min；凝血功能基本正常：INR≤1.5 ×ULN，APTT ≤1.5 ×ULN；心脏功能：左心室射血分数（LVEF）≥50%；心电图基本正常，QT 间期（QTcF）男性≤450 ms，女性≤470 ms；
8）患者必须从之前的治疗毒性中恢复至≤1级，除了脱发和2级既往含铂治疗相关神经病变（CTCAE 5.0）；
9）能合作观察不良事件和疗效，试验开始至结束期间进行PET-CT检查。

其他恶性实体肿瘤的纳入标准
1）自愿参加本次临床试验，理解研究程序且已签署知情同意；
2）年龄：18~75周岁的患者；
3）病理学诊断为晚期恶性实体肿瘤患者；
4）按东部肿瘤合作组织（ECOG）标准，体能状态为0~2分；
5）预期生存期不少于3个月；
6）根据RECIST1.1版实体肿瘤疗效评价标准，患者至少有一处PET-CT可测量病灶，要求最长径≥10 mm（若为淋巴结，则要求短轴≥15 mm）（脑转移病灶不作为唯一可测量病灶）；
7）受试者必须具有适当的器官功能，入组前符合下列实验室检查结果：骨髓储备基本正常：中性粒细胞绝对计数≥1.5×10^9/L ，血小板≥100×10^9/L ，以及血红蛋白≥80g/L；肝脏功能基本正常：血清中白蛋白≥3.0 g/dL ；胆红素≤1.5×ULN，ALT 和AST ≤2.5×ULN，如有肝转移，则ALT 或AST≤5×ULN；肾功能正常：肌酐≤1.5 倍ULN 或24 小时肌酐清除率≥60 mL/min；凝血功能基本正常：INR≤1.5 ×ULN，APTT ≤1.5 ×ULN；心脏功能：左心室射血分数（LVEF）≥50%；心电图基本正常，QT 间期（QTcF）男性≤450 ms，女性≤470 ms；
8）患者必须从之前的治疗毒性中恢复至≤1级，除了脱发和2级既往含铂治疗相关神经病变（CTCAE 5.0）；
9）能合作观察不良事件和疗效，试验开始至结束期间进行PET-CT检查。

Inclusion criteria

Inclusion criteria for liver cancer
1) 18 to 75 years old, regardless of gender; 
2) Patients with advanced hepatocellular carcinoma (inoperable or metastatic) diagnosed by histology/cytology and imaging and lack of standard treatment or do not have standard treatment conditions; 
3) Child-pugh liver function rating: Grade A, Grade B; 
4) PET-CT examination at least one measurable lesion (according to RECIST1.1 standard); 
5) Before enrollment, patients received at least 4 weeks or more than 5 half-lives after the last anti-tumor treatment; more than 1 month after palliative surgery; 
6) Expected survival time >= 3 months; 
7) End-stage liver disease model (MELD) score < 9 points;
8) Able to cooperate to observe adverse events and curative effects, and perform PET-CT examinations from the beginning to the end of the trial;
9) No other anti-tumor concomitant therapy (including steroid drugs);
10) ECOG score <= 2;
11) Serum albumin >= 30g/L, serum ALT <= 190U/L, AST <= 200 U/L, serum TBIL<= 1.5 x ULN, electrolytes are normal or normal after treatment, proteinuria=0~1+, blood creatinine <= 1.5 x ULN;
12) Routine blood examination standards should meet: HB >= 80g/L; ANC >= 1.5 x 10^9/L; PLT >= 70 x 10^9/L;
13) The patient voluntarily signs a written informed consent.

Inclusion criteria for lung cancer
1) Volunteer to participate in this clinical trial, understand the research procedures and have signed informed consent;
2) Age: 18~75 years old male or female patients;
3) Pathological and imaging diagnosis of patients with advanced lung cancer;
4) According to the Eastern Cooperative Oncology (ECOG) standard, the physical status is 0~2 points;
5) Expected survival period is not less than 3 months;
6) According to the RECIST 1.1 version of the solid tumor efficacy evaluation standard, the patient has at least one PET-CT measurable lesion with the longest diameter >= 10 mm (if it is a lymph node, the short axis >= 15 mm) (brain metastasis is not the only possible lesion Measure lesions);
7) Subjects must have appropriate organ functions and meet the following laboratory test results before entry: bone marrow reserves are basically normal: absolute neutrophil count >= 1.5 x 10^9/L, platelets >= 100 x 10^9/L, and hemoglobin >= 80g /L; liver function is basically normal: serum albumin >= 3.0 g/dL; bilirubin <= 1.5 x ULN, ALT and AST <= 2.5 x ULN, if there is liver metastasis, ALT or AST <= 5 x ULN; renal function Normal: Creatinine <= 1.5 times ULN or 24-hour creatinine clearance >= 60 mL/min; coagulation function is basically normal: INR <= 1.5 x ULN, APTT <= 1.5 x ULN; heart function: left ventricular ejection fraction (LVEF) >= 50% ; ECG is basically normal, QT interval (QTcF) male <= 450 ms, female <= 470 ms;
8) Patients must recover from previous treatment toxicity to <= 1 grade, except for hair loss and grade 2 neuropathy related to previous platinum-containing therapy (CTCAE 5.0);
9) Can cooperate to observe adverse events and curative effects, and perform PET-CT examinations from the beginning to the end of the trial.

Inclusion criteria for other malignant solid tumors
1) Volunteer to participate in this clinical trial, understand the research procedures and have signed informed consent;
2) Age: Patients between 18 and 75 years old;
3) Pathologically diagnosed as patients with advanced malignant solid tumors;
4) According to the Eastern Cooperative Oncology (ECOG) standard, the physical status is 0~2 points;
5) The expected survival period is not less than 3 months;
6) According to the RECIST 1.1 version of the solid tumor efficacy evaluation standard, the patient has at least one PET-CT measurable lesion with the longest diameter >= 10 mm (if it is a lymph node, the short axis >= 15 mm) (brain metastasis is not the only possible lesion Measure the lesion);
7) Subjects must have appropriate organ functions and meet the following laboratory test results before entry: bone marrow reserves are basically normal: absolute neutrophil count >= 1.5 x 10^9/L, platelets >= 100 x 10^9/L, and hemoglobin >= 80g /L; liver function is basically normal: serum albumin >= 3.0 g/dL; bilirubin <= 1.5 x ULN, ALT and AST <= 2.5 x ULN, if there is liver metastasis, ALT or AST<= 5 x ULN; renal function Normal: Creatinine <= 1.5 times ULN or 24-hour creatinine clearance >= 60 mL/min; coagulation function is basically normal: INR <= 1.5 x ULN, APTT <= 1.5 x ULN;heart function: left ventricular ejection fraction (LVEF) >= 50% ; the electrocardiogram is basically normal, QT interval (QTcF) male <= 450 ms, female <= 470 ms;
8) Patients must recover from the previous treatment toxicity to <= 1 grade, except for hair loss and grade 2 neuropathy related to previous platinum-containing therapy (CTCAE 5.0);
9) Cooperated to observe adverse events and curative effects, and perform PET-CT examinations from the beginning to the end of the trial.

排除标准：

肝癌的排除标准
1）严重肝硬化，肝萎缩，门静脉高压，中等量以上腹水；
2）既往有肝移植病史；
3）弥漫型肝癌，门静脉主干出现癌栓或肝阻塞性黄疸以及肝功能衰竭，出现难以控制的肝性脑病；
4）二重癌及多重癌患者；
5）有活动性上消化道溃疡、明显呕吐、慢性腹泻、肠梗阻、吸收障碍等或其他已知会影响药物吸收、分布、代谢或清除的患者；
6）之前抗癌治疗的毒性反应尚未恢复至I级或尚未从之前的手术中完全恢复；
7）有活动性出血或凝血功能异常（PT>16s、APTT>43s、TT>21s、INR≥2）、具有出血倾向或正在接受溶栓或抗凝治疗；
8）同时服用可能延长QTc和/或 Tdp的药物或影响药物代谢的药物（如镇静剂）；
9）疑似药物及其代谢物或其药用辅料有过敏史者；
10）怀孕或者哺乳期女性患者，或试验期间不愿意避孕者；
11）任何显著的临床和实验室异常，研究者认为影响安全性评价者；
12）脑转移、脑膜转移或各种精神障碍者；
13）肾小球滤过率明显异常者（内生肌酐清除率<60ml/min，血清肌酐≥1.5×ULN）；
14）正在接受广谱抗病毒药物治疗，如金刚烷胺、阿昔洛韦、更昔洛韦、利巴韦林等；抗乙肝病毒治疗患者需停药3天；
15）自身免疫疾病者；
16）HIV、HCV、HDV感染者；
17）在试验前3月内参加了任何药物或医疗器械临床试验者；正在进行其他抗肿瘤药物治疗。

肺癌的排除标准：
1）对药用辅料有过敏史者；
2）在首次给药前30天内服用过其他正在临床试验的药物，正在进行其他抗肿瘤药物治疗；
3）除了肺癌之外，近5年内还被诊断有另外一种恶性肿瘤者（不包括已经治愈的恶性肿瘤，如完全切除的基底细胞癌和原位癌）；
4）首次使用研究药物之前2周内接受过重大外科治疗、切开活检或明显创伤性损伤者。在所有情况下，患者必须在治疗开始前充分恢复及稳定；
5）受试者具有活动性胃肠道疾病或其他疾病可能导致明显影响药物吸收分布，代谢或排泄的因素；
6）无法控制的慢性系统性合并疾病（如严重的慢性肺部，肝脏，肾脏或心脏疾病）；
7）按NYHA标准，III~IV 级心功能不全者；
8）基线期心电图QTc 延长者（QTcF：男性>450 ms，女性>470 ms）；
9）任何无法控制的严重的与临床研究相关的问题（例如物质滥用，不受控制的精神病状态，不能控制的胸腔积液和/或心包积液，不受控的并发症，包括活动性感染、动脉血栓形成和症状性肺栓塞）；
10）存在间质性肺病、药物诱导的间质性肺病、需要类固醇治疗的放射性肺炎的既往病史，或者任何临床活性期间质性肺病证据；
11）受试者正处于急性感染期并需要药物治疗、抗病毒治疗；
12）受试者HIV、HBV 和HCV检测阳性（HBV病毒拷贝数≧104拷贝/mL，HCV病毒拷贝数≧103拷贝/mL）；
13）经研究者判断，客观条件（包括患者心理状态，家庭关系，社会因素或地域因素等）使患者无法完成计划研究的或受试者有其他可能导致本研究被迫中途终止的因素；
14）妊娠期或哺乳期女性；
15）自身免疫疾病。

其他恶性实体肿瘤的排除标准：
1）对药用辅料有过敏史者；
2）在首次给药前30天内服用过其他正在临床试验的药物，正在进行其他抗肿瘤药物治疗；
3）近5年内还被诊断有另外一种恶性实体肿瘤者（不包括已经治愈的恶性肿瘤，如完全切除的基底细胞癌和原位癌）；
4）首次使用研究药物之前2周内接受过重大外科治疗、切开活检或明显创伤性损伤者。在所有情况下，患者必须在治疗开始前充分恢复及稳定；
5）受试者具有活动性胃肠道疾病或其他疾病可能导致明显影响药物吸收分布，代谢或排泄的因素；
6）无法控制的慢性系统性合并疾病（如严重的慢性肺部，肝脏，肾脏或心脏疾病）；
7）按NYHA标准，III~IV 级心功能不全者；
8）基线期心电图QTc 延长者（QTcF：男性>450 ms，女性>470 ms）；
9）任何无法控制的严重的与临床研究相关的问题（例如物质滥用，不受控制的精神病状态，不能控制的胸腔积液和/或心包积液，不受控的并发症，包括活动性感染、动脉血栓形成和症状性肺栓塞）；
10）受试者正处于急性感染期并需要药物治疗、抗病毒治疗；
12）受试者HIV、HBV 和HCV检测阳性（HBV病毒拷贝数≧104拷贝/mL，HCV病毒拷贝数≧103拷贝/mL）；
13）经研究者判断，客观条件（包括患者心理状态，家庭关系，社会因素或地域因素等）使患者无法完成计划研究的或受试者有其他可能导致本研究被迫中途终止的因素；
14）妊娠期或哺乳期女性；
15）自身免疫疾病。

Exclusion criteria：

Exclusion criteria for liver cancer
1) Severe liver cirrhosis, liver atrophy, portal hypertension, moderate or above ascites;
2) Past medical history of liver transplantation;
3) Diffuse liver cancer, tumor thrombus or hepatic obstructive jaundice in the trunk of the portal vein, liver failure, and uncontrollable hepatic encephalopathy;
4) Patients with double cancer and multiple cancers;
5) Patients with active upper gastrointestinal ulcers, obvious vomiting, chronic diarrhea, intestinal obstruction, malabsorption, etc. or other patients who are known to affect drug absorption, distribution, metabolism or clearance;
6) The toxicity of the previous anti-cancer treatment has not recovered to grade I or has not fully recovered from the previous surgery;
7) Active bleeding or abnormal blood coagulation (PT > 16s, APTT > 43s, TT > 21s, INR >= 2), have bleeding tendency or are receiving thrombolysis or anticoagulation therapy;
8) At the same time taking drugs that may prolong QTc and/or Tdp or drugs that affect drug metabolism (such as tranquilizers);
9) Suspected drug and its metabolites or pharmaceutical excipients with a history of allergies;
10) Pregnant or breastfeeding female patients, or those who are unwilling to use contraception during the trial;
11) Any significant clinical and laboratory abnormalities that the investigator believes will affect the safety evaluator;
12) People with brain metastases, meningeal metastases, or various mental disorders;
13) Patients with significantly abnormal glomerular filtration rate (endogenous creatinine clearance rate < 60ml/min, serum creatinine >= 1.5 x ULN);
14) Being treated with broad-spectrum antiviral drugs, such as amantadine, acyclovir, ganciclovir, ribavirin, etc.; anti-hepatitis B virus treatment patients need to stop the drug for 3 days;
15) Autoimmune disease;
16) People infected with HIV, HCV, HDV;
17) Participated in any drug or medical device clinical trial within 3 months before the trial; other anti-tumor drug treatments are in progress.

Exclusion criteria for lung cancer:
1) People with a history of allergies to pharmaceutical supplements;
2) Have taken other drugs in clinical trials within 30 days before the first administration, and are undergoing other anti-tumor drug treatments;
3) In addition to lung cancer, people who have been diagnosed with another type of malignant tumor in the past 5 years (excluding cured malignant tumors, such as completely resected basal cell carcinoma and carcinoma in situ);
4) Those who have received major surgical treatment, open biopsy, or obvious traumatic injury within 2 weeks before using the study drug for the first time. In all cases, the patient must fully recover and stabilize before treatment begins;
5) Subjects have active gastrointestinal diseases or other diseases that may cause factors that significantly affect drug absorption, distribution, metabolism or excretion;
6) Uncontrollable chronic systemic complications (such as severe chronic lung, liver, kidney or heart disease);
7) According to NYHA standards, patients with grade III~IV cardiac insufficiency;
8) Patients with prolonged QTc of baseline ECG (QTcF: male > 450 ms, female > 470 ms);
9) Any uncontrollable serious clinical research related problems (such as substance abuse, uncontrolled psychosis, uncontrollable pleural effusion and/or pericardial effusion, uncontrolled complications, including active infection, arterial Thrombosis and symptomatic pulmonary embolism);
10) A history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy, or any evidence of qualitative lung disease during clinical activity;
11) The subject is in an acute infection period and needs drug treatment and antiviral treatment;
12) The subjects tested positive for HIV, HBV and HCV (HBV virus copy number >= 10^4 copies/mL, HCV virus copy number >= 10^3 copies/mL);
13) According to the judgment of the investigator, objective conditions (including the patient's mental state, family relationship, social factors or geographical factors, etc.) prevent the patient from completing the planned study or the subject has other factors that may cause the study to be terminated midway;
14) Women who are pregnant or breastfeeding;
15) Autoimmune diseases.

Exclusion criteria for other malignant solid tumors:
1) Those who have a history of allergy to pharmaceutical excipients;
2) Have taken other drugs in clinical trials within 30 days before the first administration, and are undergoing other anti-tumor drug treatment;
3) Those who have been diagnosed with another type of malignant solid tumor in the past 5 years (excluding cured malignant tumors, such as completely resected basal cell carcinoma and carcinoma in situ);
4) Those who have received major surgical treatment, open biopsy, or obvious traumatic injury within 2 weeks before using the study drug for the first time. In all cases, the patient must fully recover and stabilize before treatment begins;
5) Subjects have active gastrointestinal diseases or other diseases that may cause factors that significantly affect drug absorption, distribution, metabolism or excretion;
6) Uncontrollable chronic systemic complications (such as severe chronic lung, liver, kidney or heart disease);
7) According to NYHA standards, patients with grade III~IV cardiac dysfunction;
8) Patients with prolonged QTc of baseline ECG (QTcF: male > 450 ms, female > 470 ms);
9) Any uncontrollable serious clinical research related problems (such as substance abuse, uncontrolled psychosis, uncontrollable pleural effusion and/or pericardial effusion, uncontrolled complications, including active infection, arterial Thrombosis and symptomatic pulmonary embolism);
10) The subject is in an acute phase of infection and requires drug treatment and antiviral treatment;
12) The subjects tested positive for HIV, HBV and HCV (HBV virus copy number >= 10^4 copies/mL, HCV virus copy number >= 10^3 copies/mL);
13) According to the judgment of the investigator, objective conditions (including the patients mental state, family relationship, social factors or geographical factors, etc.) prevent the patient from completing the planned study or the subject has other factors that may cause the study to be terminated midway;
14) Women who are pregnant or breastfeeding;
15) Autoimmune disease.

研究实施时间：

Study execute time：

从 From 2020-12-31 00:00:00至 To 2022-12-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2021-03-01 00:00:00 至 To 2022-12-31 00:00:00

干预措施：

Interventions：

组别：	1	样本量：	30
Group：	1	Sample size：	30
干预措施：	新型溶瘤病毒+安罗替尼组	干预措施代码：
Intervention：	Oncolytic virus + Anlotinib	Intervention code：

组别：	2	样本量：	30
Group：	2	Sample size：	30
干预措施：	新型溶瘤病毒	干预措施代码：
Intervention：	Oncolytic virus	Intervention code：

组别：	3	样本量：	30
Group：	3	Sample size：	30
干预措施：	安罗替尼组	干预措施代码：
Intervention：	Anlotinib	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	广西	市(区县)：
Country：	China	Province：	Guangxi Zhuang Autonomous Region	City：
单位(医院)：	广西中医药大学第一附属医院	单位级别：	三级甲等
Institution hospital：	The First Affiliated Hospital of Guangxi University of traditional Chinese Medicine	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	疾病控制率	指标类型：	主要指标
Outcome：	Disease Control Rate, DCR	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	指标类型：	主要指标
Outcome：	Safety	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	肿瘤进展时间	指标类型：	次要指标
Outcome：	Time-To-Progression, TTP	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	客观有效率	指标类型：	次要指标
Outcome：	Objective Response Rate, ORR	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	症状缓解率	指标类型：	次要指标
Outcome：	Remission 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：	生活质量	指标类型：	次要指标
Outcome：	Quality of Life	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：

标本中文名：	尿液	组织：
Sample Name：	urine	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：	粪便	组织：
Sample Name：	feces	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	75	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

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

Single arm

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）：	原始数据上报国家科技部系统共享
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	The original data is reported to the Ministry of Science and Technology for system sharing
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：	对记录在病例报告表(CRF)的信息，尤其是安全性和疗效有关的关键信息和病人的原始记录是否吻合。数据管理 1、管理（1）建立数据管理委员会，招聘熟练计算机操作人员组建数据管理委员会，由本课题组成员担任组长，其余数据管理人员均对该研究方案不知情。（2）数据保存与录入所有受试者数据及量表资料由DDC组员进行电脑录入，将原始资料全部录入保存在课题数据库，该数据库录入内容与原始资料保持一致。纸质资料专人管理。（3）数据质控与备份课题组成员定期对录入数据进行质控，及时报告、记录数据缺失项，对明显错误数据重新核对、校准。定期导出、备份数据至物理存储装置，专人保管，防治数据库损坏。
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	data acquisition The research medical record is the most original record and must be kept properly. In this study, electronic case report form was used to collect data. The case report form is from the study medical record and completed by the investigator. The case report form must be completed for each screened and selected case. Researchers will ensure the accuracy and reliability of data collection. All data will be recorded by Internet based electronic CRF, and the integrity of data will be checked automatically online. After entering the user name and password, the research data can be obtained, and the user should keep his password strictly confidential. The electronic communication between the server and the user's personal computer is encrypted, and the protected data (patient name, address, ID number, etc.) will not be transmitted. A complete audit trail is available for all changes to study data. Laboratory data will be confirmed using a range of normal values depending on the center and gender. Descriptive and logical data check is carried out in the constantly improved database. Any unreasonable or inconsistent data input will be informed to the research unit and / or the inspector, and the staff of the research unit will explain and correct it. The researchers must make a decision on the classification of toxic reactions and the response of tumor efficacy, and the main researchers should make a final judgment on the diagnosis. During the research process, the investigator shall allow the sponsor's inspectors or representatives to inspect the research related documents (such as the informed consent of patients, the inventory of research drugs, and the approval documents of the ethics committee) in the research institution. During the visit, the inspectors will strictly review the patient's files to check whether the information recorded in the CRF, especially the key information related to safety and efficacy, is consistent with the original record of the patient. data management 1, management (1) Establish a data management committee, recruit skilled computer operators to establish a data management committee, with the members of the research group as the team leader, and the rest of the data management personnel are unaware of the research scheme. (2) Data saving and inputting all subjects' data and scale data shall be input by DDC team members by computer, and all the original data shall be input and saved in the subject database, and the input content of the database shall be consistent with the original data. Paper materials shall be managed by special personnel. (3) The members of the data quality control and backup research group regularly control the input data, timely report and record the missing items of the data, and recheck and calibrate the obviously wrong data. Regularly export and backup the data to the physical storage device, and assign special personnel to keep it to prevent database damage.
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2021-02-24 08:51:33