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：	ChiCTR2400094961
最近更新日期： Date of Last Refreshed on：	2024-12-31 09:04:13
注册时间： Date of Registration：	2024-12-31 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	依沃西单抗联合白蛋白紫杉醇序贯空间放疗治疗晚期实体瘤的有效性和安全性的单臂、开放、Ⅱ期临床研究
Public title：	A single-arm, open-label Phase II clinical study on the efficacy and safety of Ivosidenib combined with Nab-paclitaxel sequentially followed by spatially fractionated radiotherapy in the treatment of advanced solid tumors
注册题目简写：
English Acronym：
研究课题的正式科学名称：	依沃西单抗联合白蛋白紫杉醇序贯放疗治疗晚期实体瘤的有效性和安全性的单臂、开放、Ⅱ期临床研究
Scientific title：	A single-arm, open-label Phase II clinical study on the efficacy and safety of Ivosidenib combined with Nab-paclitaxel sequentially followed by radiotherapy in the treatment of advanced solid tumors
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：	石翔翔	研究负责人：	林盛
Applicant：	Shi Xiangxiang	Study leader：	Lin Sheng
申请注册联系人电话： Applicant telephone：	+86 139 8276 8045	研究负责人电话： Study leader's telephone：	+86 151 0818 7773
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：	uiokjh@163.com	研究负责人电子邮件： Study leader's E-mail：	lslinsheng@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：	四川省泸州市江阳区太平街25号	研究负责人通讯地址：	四川省泸州市江阳区太平街25号
Applicant address：	25 Taiping Street, Luzhou, Sichuan, China	Study leader's address：	25 Taiping Street, Luzhou, Sichuan, 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：	西南医科大学附属医院肿瘤科
Applicant's institution：	Department of Oncology, Affiliated Hospital of Southwest Medical University
研究负责人所在单位：	西南医科大学附属医院肿瘤科
Affiliation of the Leader：	Department of Oncology, Affiliated Hospital of Southwest Medical 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：	KY2024485	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：	西南医科大学附属医院临床试验伦理委员会
Name of the ethic committee：	Clinical Trial Ethics Committee of Affiliated Hospital of Southwest Medical University
伦理委员会批准日期： Date of approved by ethic committee：	2024-12-09 00:00:00
伦理委员会联系人：	张增瑞
Contact Name of the ethic committee：	Zhang Zengrui
伦理委员会联系地址：	四川省泸州市太平街25号
Contact Address of the ethic committee：	25 Taiping Street, Luzhou, Sichuan
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 830 316 5273	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：

西南医科大学附属医院肿瘤科

Primary sponsor：

Department of Oncology, Affiliated Hospital of Southwest Medical University

研究实施负责（组长）单位地址：

四川省泸州市太平街25号

Primary sponsor's address：

25 Taiping Street, Luzhou, Sichuan

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	四川	市(区县)：	泸州
Country：	China	Province：	Sichuan	City：	Luzhou
单位(医院)：	西南医科大学附属医院肿瘤科	具体地址：	四川省泸州市太平街25号
Institution hospital：	Department of Oncology, Affiliated Hospital of Southwest Medical University	Address：	25 Taiping Street, Luzhou, Sichuan

经费或物资来源：

科研基金

Source(s) of funding：

scientific-research funding

研究疾病：

晚期实体肿瘤

Target disease：

advanced solid 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期临床试验

Study phase：

2

研究设计：

单臂

Study design：

Single arm

研究目的：

探索依沃西单抗联合白蛋白紫杉醇序贯空间放疗治疗晚期实体瘤的有效性和安全性

Objectives of Study：

Explore the efficacy and safety of Evocimab combined with nab-paclitaxel followed by sequential spatially fractionated radiotherapy in the treatment of advanced solid tumors.

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. Male or female, aged 18 to 75 years inclusive.
2. Voluntarily sign a written informed consent form.
3. Histologically confirmed patients with advanced cancer in the post-line setting, as demonstrated by enhanced CT, cranial MRI, abdominal ultrasound, or PET-CT.
4. Failed after three or more lines of standard treatment, with an expected lifespan greater than 3 months.
5. Have at least one measurable tumor lesion according to RECIST 1.1.
6. Have an ECOG score of 0 or 1.
7. Have an expected survival duration of >=3 months.
8. Have been off radiotherapy, chemotherapy, hormone therapy, and molecular targeted therapy for more than 8 weeks, with all treatment-related adverse events resolved to baseline.
9. Have good major organ function:
a) Hematology (without any blood component or cytokine growth factor support therapy within 7 days before starting the study treatment):
i. Absolute neutrophil count (ANC) >= 1.5 × 10^9/L (1,500/mm³).
ii. Platelet count >= 100 × 10^9/L (100,000/mm³).
iii. Hemoglobin >= 90 g/L.
b) Renal:
i. Calculated creatinine clearance (CrCl) >= 50 mL/min using the Cockcroft-Gault formula.
* CrCl (mL/min) = [(140 - age) × weight (kg) × F] / (SCr (mg/dL) × 72), where F=1 for males and F=0.85 for females; SCr = serum creatinine.
ii. Urine protein < 2+ or 24-hour urine protein < 1.0 g.
c) Liver:
i. Total bilirubin (TBil) <= 1.5 × ULN.
ii. AST and ALT <= 2.5 × ULN.
iii. For subjects with liver metastases, TBil <= 3 × ULN; ALT and AST <= 5 × ULN.
d) Coagulation:
i. International normalized ratio (INR) and activated partial thromboplastin time (APTT) <= 1.5 × ULN.
10. Female subjects of reproductive potential must have a negative serum pregnancy test within 3 days before the first dose. If a female subject of reproductive potential engages in sexual activity with a non-sterilized male partner, she must use an acceptable method of contraception starting from screening and must agree to continue using it for 6 months after the last dose of the study drug; the decision to discontinue contraception after this point should be discussed with the investigator.
11. Subjects are willing and able to comply with the scheduled visits, treatment regimen, laboratory tests, and other study requirements.

排除标准：

主要排除标准： 1) 首次依沃西单抗给药前4周内参加过试验性药物的治疗或使用过试验性器械。 2) 入组前3年内患有其他活动性恶性肿瘤。除外局部可治愈恶性肿瘤（表现为已治愈），如基底或皮肤鳞状细胞癌、浅表膀胱癌、子宫内膜、宫颈或乳房原位癌。 3) 同时入组另一项临床研究，除非其为一项观察性（非干预性）临床研究或干预性研究的随访期（定义为首次用药时间距离前一项临床研究末次用药时间达4周以上或该研究药物的5个半衰期以上，以最长为准）。 4) 研究治疗开始前两年内需要系统治疗的活动性自身免疫性疾病，或研究者判断存在可能复发或计划治疗的自身免疫性疾病；以下除外：不需系统治疗的皮肤病（如：白癜风、脱发、银屑病或湿疹）；由自身免疫性甲状腺炎引起的甲状腺功能减退，仅需要稳定剂量的激素替代治疗；控制良好的I型糖尿病；童年期哮喘已完全缓解，成人后无需任何干预的受试者；研究者判断所患疾病在无外部触发因素的情况下不会复发。 5) 伴有活动性或需要临床治疗的炎症性肠病（如克罗恩病、溃疡性结肠炎或慢性腹泻）。 6) 受试者在服用研究药物后14天内需要使用皮质类固醇（>10mg每日强的松当量）或其他免疫抑制药物进行全身治疗。在没有活动性自身免疫疾病的情况下，允许吸入或外用类固醇和肾上腺替代剂量>10mg每日强的松当量。受试者允许使用局部、眼部、关节内、鼻内和吸入性皮质类固醇（全身吸收最小）。系统性皮质类固醇的生理替代剂量是允许的，即使>10毫克/天的强的松当量。允许短期使用皮质类固醇预防（如对比剂过敏）或治疗非自身免疫性疾病（如接触性过敏原引起的迟发型超敏反应）。 7) 肉瘤患者既往接受过抗血管抑制剂（如：贝伐单抗、安罗替尼、培唑帕尼、瑞戈非尼等）、黑色素瘤患者排除BRAF V600E突变使用靶向药（达拉非尼+曲美替尼、维莫非尼+Cobimetinib、司美替尼）。 8) 已知人类免疫缺陷病毒或已知获得性免疫缺陷综合症检测呈阳性的病史。 9) 已知异体器官移植史和异体造血干细胞移植史。 10) 已知存在间质性肺病或病史。 11) 受试者入组前4周内检查发现有坏死性病灶，研究者判断有大出血风险。 12) 首次给药前4周内发生严重感染，包括但不局限于伴有需要住院治疗的并发症、败血症或严重肺炎。 13) 已知患有活动性肺结核（TB）。怀疑有活动性TB的受试者，需检查胸部X线、痰液以及通过临床症状和体征排除。 14) 未治疗的慢性乙型肝炎患者或慢性乙型肝炎病毒（HBV）携带者且HBV DNA＞1000IU/mL，及活动性丙型肝炎患者应排除。非活动性乙型肝炎表面抗原（HbsAg）携带者，经治疗且稳定的乙型肝炎患者（HBV DNA<1000IU/mL），以及已治愈的丙型肝炎患者可以入组。对于HCV Ab阳性的受试者，仅在HCV RNA检测结果呈阴性的情况下，才有资格参与研究。 15) 在依沃西单抗首次给药前的4周内接受过最后一次放疗或抗肿瘤治疗（化疗、靶向治疗、用于控制肿瘤疾病的中草药或肿瘤栓塞术等）。 16) 在依沃西单抗首次给药前的30天内进行重大外科手术，或尚未从既往手术中完全恢复。允许进行局部手术（如全身性端口的放置、芯针活检和前列腺活检），前提是该手术在研究治疗药物首次给药时的至少24小时之前完成。 17) 已知存在脑膜转移、脊髓压迫、软脑膜疾病或活动性脑转移。但允许符合以下要求且中枢神经系统之外存在可测量病灶的受试者入组：1）既往未经治疗，目前无症状（如无神经功能障碍、癫痫或其它典型中枢神经系统转移症状和体征；不需要糖皮质激素治）；2）经过治疗后无症状在研究治疗开始前影像学稳定至少4周（如无新的或扩大的脑转移病灶），且已经停止全身性糖皮质激素和抗惊厥药物治疗至少2周。 18) 根据研究者的判断，采用反复引流或其他方法仍然无法稳定控制的胸腔积液、心包积液或腹水的受试者。 19) 未得到控制的并发疾病，包括症状性充血性心力衰竭（按照纽约心脏病协会功能分级确定的3或4级）、未得到控制的高血压、不稳定型心绞痛、控制不佳的心律失常、急性或正患有心肌缺血的证据、重度活动性消化性溃疡病或胃炎，或会限制受试者依从研究要求或影响受试者提供书面知情同意能力的精神疾病/社会状况。入组前6个月内发生过任何动脉血栓栓塞事件，包括心肌梗死、脑血管意外或短暂性脑缺血发作，有深静脉血栓、肺栓塞或其它任何严重血栓栓塞的病史。 20) 既往抗肿瘤治疗毒性未缓解，定义为毒性未恢复至NCI CTCAE 5.0版的0级或1级，或入选/排除标准中规定的水平，但脱发除外。对于发生不可逆毒性且预期研究药物给药后不会加重的受试者（例如听力损失），在与医学监察员协商后，可能会被纳入研究。放疗引起的远期毒性，经研究者判断不能恢复的受试者，在与医学监察员协商后，可能会被纳入研究。 21) 在依沃西单抗首次给药前的30天内接种了活疫苗，或计划在研究期间接种活疫苗。 22) 既往放疗无效或进展者。 23) 既往接受过区域放疗，经评估不能再行大分割放疗。 24) 已知对其他单克隆抗体产生严重超敏反应的病史。 25) 已知对依沃西单抗制剂的任何成分过敏。 26) 妊娠期或哺乳期女性。 27) 研究者认为可能会导致接受研究药物治疗有风险，或将干扰研究药物的评价或受试者安全性或研究结果解析的任何状况。

Exclusion criteria：

1. Participation in treatment with experimental drugs or use of experimental devices within 4 weeks prior to the first administration of Evocimab. 2. History of other active malignancies within 3 years before enrollment, except for locally curable malignancies (demonstrated as cured) such as basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the endometrium, cervix, or breast. 3. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study (defined as more than 4 weeks or more than 5 half-lives of the study drug from the last dose of the previous clinical study, whichever is longer). 4. Active autoimmune diseases requiring systemic treatment within 2 years before the start of study treatment, or autoimmune diseases that the investigator judges may recur or plan to treat; exceptions include: dermatological conditions not requiring systemic treatment (e.g., vitiligo, alopecia, psoriasis, or eczema); hypothyroidism due to autoimmune thyroiditis requiring only stable-dose hormone replacement therapy; well-controlled Type 1 diabetes; childhood asthma that has fully resolved and requires no intervention in adulthood; and diseases judged by the investigator as unlikely to recur without external triggers. 5. Presence of active or clinically significant inflammatory bowel disease (such as Crohn's disease, ulcerative colitis, or chronic diarrhea). 6. Subjects requiring systemic treatment with corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive drugs within 14 days after starting study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalent are allowed in the absence of active autoimmune disease. Subjects may use local, ocular, intra-articular, intranasal, and inhaled corticosteroids (with minimal systemic absorption). Physiological replacement doses of systemic corticosteroids are allowed, even if >10 mg/day prednisone equivalent. Short-term use of corticosteroids for prophylaxis (e.g., contrast dye allergy) or treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reactions due to contact allergens) is permitted. 7. Sarcoma patients who have previously received anti-angiogenic inhibitors (such as bevacizumab, anlotinib, pazopanib, regorafenib, etc.), and melanoma patients with BRAF V600E mutations excluding the use of targeted therapies (dabrafenib + trametinib, vemurafenib + cobimetinib, selumetinib). 8. Known history of positive testing for human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS). 9. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation. 10. Known interstitial lung disease or history of interstitial lung disease. 11. Subjects with necrotic lesions detected within 4 weeks before enrollment, and the investigator judges there to be a risk of significant bleeding. 12. Severe infections occurring within 4 weeks before the first dose, including but not limited to those with complications requiring hospitalization, sepsis, or severe pneumonia. 13. Known active tuberculosis (TB). Subjects suspected of having active TB require chest X-ray, sputum examination, and exclusion based on clinical symptoms and signs. 14. Untreated chronic hepatitis B patients or chronic hepatitis B virus (HBV) carriers with HBV DNA >1000 IU/mL, and patients with active hepatitis C should be excluded. Non-active hepatitis B surface antigen (HbsAg) carriers, treated and stable hepatitis B patients (HBV DNA <1000 IU/mL), and cured hepatitis C patients may be enrolled. For subjects with positive HCV Ab, eligibility for participation is contingent on a negative HCV RNA test result. 15. Subjects who received their last radiotherapy or antitumor treatment (chemotherapy, targeted therapy, traditional Chinese medicine for tumor control, or tumor embolization, etc.) within 4 weeks before the first dose of Evocimab. 16. Subjects who underwent major surgery within 30 days before the first dose of Evocimab or have not fully recovered from previous surgery. Local surgeries (such as placement of systemic ports, core needle biopsies, and prostate biopsies) are allowed if completed at least 24 hours before the first dose of the study treatment drug. 17. Known presence of leptomeningeal metastasis, spinal cord compression, leptomeningeal disease, or active brain metastases. However, subjects with measurable lesions outside the central nervous system may be enrolled if they meet the following criteria: 1) untreated and asymptomatic (no neurological dysfunction, seizures, or other typical symptoms and signs of central nervous system metastases; no requirement for glucocorticoid therapy); 2) asymptomatic after treatment and radiologically stable for at least 4 weeks before the start of study treatment (no new or enlarged brain metastases), and have discontinued systemic glucocorticoid and anticonvulsant medications for at least 2 weeks. 18. Subjects with pleural effusion, pericardial effusion, or ascites that cannot be stably controlled by repeated drainage or other methods, as judged by the investigator. 19. Uncontrolled concurrent diseases, including symptomatic congestive heart failure (New York Heart Association functional class 3 or 4), uncontrolled hypertension, unstable angina pectoris, uncontrolled arrhythmias, evidence of acute or ongoing myocardial ischemia, severe active peptic ulcer disease or gastritis, or psychiatric/social conditions that would limit the subject's ability to comply with study requirements or affect their ability to provide written informed consent. Any arterial thromboembolic event within 6 months before enrollment, including myocardial infarction, cerebrovascular accident, or transient ischemic attack, and a history of deep venous thrombosis, pulmonary embolism, or any other serious thromboembolic event. 20. Unresolved toxicity from previous antitumor treatment, defined as toxicity not returning to grade 0 or 1 according to the NCI CTCAE version 5.0 or the level specified in the inclusion/exclusion criteria, except for alopecia. Subjects with irreversible toxicity that is not expected to worsen with study drug administration may be included in the study after consultation with the medical monitor. Subjects with long-term toxicity from radiotherapy, judged by the investigator as irreversible, may be included in the study after consultation with the medical monitor. 21. Vaccination with live vaccines within 30 days before the first dose of Evocimab or plans to receive live vaccines during the study period. 22. Subjects with previous radiotherapy that was ineffective or resulted in disease progression. 23. Subjects who have undergone regional radiotherapy and are assessed as not suitable for further hypofractionated radiotherapy. 24. Known history of severe hypersensitivity reactions to other monoclonal antibodies. 25. Known allergy to any component of the Evocimab formulation. 26. Pregnant or lactating women. 27. Any condition that the investigator believes may pose a risk to the subject receiving study drug treatment or interfere with the evaluation of the study drug or the subject's safety or the interpretation of study results.

研究实施时间：

Study execute time：

从 From 2025-01-01 00:00:00至 To 2029-12-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-01-01 00:00:00 至 To 2026-12-31 00:00:00

干预措施：

Interventions：

组别：	干预组	样本量：	15
Group：	intervention group	Sample size：	15
干预措施：	空间放疗+依沃西单抗+白蛋白紫杉醇治疗	干预措施代码：
Intervention：	Ivosidenib combined with Nab-paclitaxel sequentially followed by spatially fractionated radiotherapy	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	四川省	市(区县)：	泸州市
Country：	China	Province：	Sichuan	City：	Luzhou
单位(医院)：	西南医科大学附属医院	单位级别：	三甲
Institution hospital：	Affiliated Hospital of Southwest Medical University	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	客观缓解率	指标类型：	主要指标
Outcome：	Objective remission rate, ORR	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

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

指标中文名：	缓解持续时间	指标类型：	次要指标
Outcome：	Duration of Overall Response,DOR	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	至缓解时间	指标类型：	次要指标
Outcome：	Time to Remission, TTR	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, PFS	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, OS	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：

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）：

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：	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	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）：	原始数据公开为2029年12月31日，采用excel表格或者病例记录表共享。
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	The original data will be disclosed on December 31st, 2029 and shared in excel tables or case records.
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：	数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集上传至研究者指定邮箱。
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Data collection and management consists of two parts. One is Case Record (CRF), the other is electronic collection, and the data is assigned to the researcher's email.
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2024-12-31 09:03:45