ChiCTR2300078896 版本V1.0 版本创建时间2023/12/20 16:28:52 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

ChiCTR2300078896 

最近更新日期：

Date of Last Refreshed on：

2023-12-20 16:28:30 

注册时间：

Date of Registration：

2023-12-20 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

信迪利单抗联合仑伐替尼治疗复发或转移性脑膜瘤的II期临床研究

Public title：

Phase II Study of Sintilimab Combined with Lenvatinib in the Treatment of Recurrent or Metastatic Meningiomas

注册题目简写：

English Acronym：

研究课题的正式科学名称：

信迪利单抗联合仑伐替尼治疗复发或转移性脑膜瘤的II期临床研究

Scientific title：

Phase II Study of Sintilimab Combined with Lenvatinib in the Treatment of Recurrent or Metastatic Meningiomas

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：

杜成 

研究负责人：

冯思哲 

Applicant：

Cheng Du 

Study leader：

Sizhe Feng 

申请注册联系人电话：

Applicant telephone：

+86 189 4029 6860

研究负责人电话：

Study leader's telephone：

+86 153 0988 3680

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：

767920128@qq.com

研究负责人电子邮件：

Study leader's E-mail：

Fsz2023@126.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：

沈阳市沈河区文化路83号

研究负责人通讯地址：

沈阳市沈河区文化路83号

Applicant address：

No.83, Wenhua Road, Shenhe District, Shenyang, 110016, China

Study leader's address：

No.83, Wenhua Road, Shenhe District, Shenyang, 110016, 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：

中国人民解放军北部战区总医院

Applicant's institution：

General Hospital of the Northern Theater Command of the Chinese People's Liberation Army

研究负责人所在单位：

中国人民解放军北部战区总医院

Affiliation of the Leader：

General Hospital of the Northern Theater Command of the Chinese People's Liberation Army

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

伦审Y(2023)第166号

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：

中国人民解放军北部战区总医院医学伦理委员会

Name of the ethic committee：

Medical Ethics Committee of the General Hospital of the Northern Theater Command of the Chinese People's Liberation Army

伦理委员会批准日期：

Date of approved by ethic committee：

2023-09-27 00:00:00

伦理委员会联系人：

刘宝军

Contact Name of the ethic committee：

Baojun Liu

伦理委员会联系地址：

辽宁省沈阳市沈河区文化路83号

Contact Address of the ethic committee：

No.83, Culture Road, Shenhe District, Shenyang, Liaoning Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 24 2885 6577

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：

中国人民解放军北部战区总医院

Primary sponsor：

General Hospital of the Northern Theater Command of the Chinese People's Liberation Army

研究实施负责（组长）单位地址：

辽宁省沈阳市沈河区文化路83号

Primary sponsor's address：

No.83, Culture Road, Shenhe District, Shenyang, Liaoning Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

辽宁

市(区县)：

沈阳

Country：

China

Province：

Liaoning

City：

Shenyang

单位(医院)：

中国人民解放军北部战区总医院

具体地址：

辽宁省沈阳市沈河区文化路83号

Institution
hospital：

General Hospital of the Northern Theater Command of the Chinese People's Liberation Army

Address：

No.83, Culture Road, Shenhe District, Shenyang, Liaoning Province

经费或物资来源：

无

Source(s) of funding：

No

Target disease：

Meningioma

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：

主要目的： 探索信迪利单抗联合仑伐替尼治疗复发或转移性脑膜瘤的有效性 次要目的： 探索信迪利单抗联合仑伐替尼治疗复发或转移性脑膜瘤的有效性和安全性 探索性目的： 探索可能与疗效或预后相关的肿瘤免疫标志物（包括但不限于PD-L1表达水平、肿瘤突变负荷[tumor mutation burden, TMB]等）  

Objectives of Study：

Primary objective: To explore the efficacy of Sintilimab Combined with Lenvatinib in the treatment of recurrent or metastatic meningioma Secondary objective: To explore the efficacy and safety of Sintilimab Combined with Lenvatinib in the treatment of recurrent or metastatic meningioma Exploratory objective: Explore tumor immune markers that may be related to efficacy or prognosis (including but not limited to PD-L1 expression levels, tumor mutation burden (TMB), etc.)

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

1.在任何试验相关流程实施之前，签署书面知情同意； 2.男性或女性，≥18周岁； 3. ECOG PS评分为0-2； 4.病理学确诊的2-3级脑膜瘤； 5.既往脑膜瘤手术后肿瘤复发转移或存在残留病灶（既往可接受过放疗，但需明确疾病进展，末次放疗结束至少24周）； 6.至少有1个颅内可测量病灶； 7.具有充分的器官和骨髓功能，入组前实验室检查值符合下列要求： 1)血常规：绝对中性粒细胞计数（ANC）≥1.5×109/L； 血小板计数（PLT）≥100×109/L； 血红蛋白含量（HGB）≥9.0 g/dL； 2)肝功能：血清总胆红素（TBIL）≤1.5×正常上限（ULN）；丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）和碱性磷酸酶（ALP）≤2.5×ULN； 血清白蛋白≥28 g/L； 3)肾功能：血清肌酐（Cr）≤ 1.5×ULN 或肌酐清除率（CCr）≥ 50mL/min（Cockcroft-Gault 公式）；尿常规结果显示尿蛋白<2+；对基线时尿常规检测显示尿蛋白≥2+的患者，应进行24小时尿液采集且24小时尿蛋白定量<1g； 4)凝血功能：国际标准化比率（INR）和活化部分凝血活酶时间（APTT）≤ 1.5倍ULN 8.对于育龄期女性受试者，应在接受首次研究药物给药（第1周期第1天）之前的3天内接受尿液或血清妊娠试验且结果为阴性。如果尿液妊娠试验结果无法确认为阴性，则要求进行血液妊娠试验。非育龄期女性定义为绝经后至少１年，或进行过手术绝育或子宫切除术； 9.如存在受孕风险，所有受试者（不论男性或女性）均需在整个治疗期间直至治疗末次研究药物给药后120天（或末次研究药物给药后180天）内采用年失败率低于1%的避孕措施。

Inclusion criteria

1. Signed written informed consent before the implementation of any trial-related procedures; 2. Male or female, ≥18 years old; 3. ECOG PS score 0-2; 4. Pathologically confirmed grade 2-3 meningiomas; 5. Tumor recurrence and metastasis or residual lesions after previous meningioma surgery (prior radiotherapy may have been received, but disease progression must be identified, and at least 24 weeks after the end of the last radiotherapy); 6. There was at least 1 measurable intracranial lesion; 7. It had sufficient organ and bone marrow function, and the laboratory test values before enrollment met the following requirements: 1) Blood routine: absolute neutrophil count (ANC) ≥1.5×109/L; platelet count (PLT) ≥100×109/L; hemoglobin content (HGB) ≥9.0 g/dL; 2) Liver function: serum total bilirubin (TBIL) ≤1.5× upper limit of normal (ULN); alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) ≤2.5×ULN; serum albumin ≥28 g/L; 3) Renal function: serum creatinine (Cr) ≤ 1.5×ULN or creatinine clearance (CCr) ≥ 50mL/min (Cockcroft-Gault formula); urine routine results showed urinary protein<2+; for patients with urine protein ≥2+ at baseline, 24-hour urine collection and 24-hour protein quantification should be performed<1g; 4) Coagulation function: International standardized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 times ULN; 8. For female subjects of reproductive age, a urine or serum pregnancy test should be performed negative within 3 days before receiving the first study drug administration (day 1 of the cycle ). If the results of the urine pregnancy test cannot be confirmed as negative, a blood pregnancy test is required. Women who are not in their reproductive age were defined as those who have been at least one year after menopause or have undergone surgical sterilization or hysterectomy. 9. In cases where there is a potential risk of conception, all subjects (both male and female) must utilize a contraceptive method with an annual failure rate of less than 1% throughout the entire duration of treatment, up to 120 days following the last administration of the study drug (or 180 days after the final administration of the study drug).

排除标准：

1.在首次给药前5年内诊断为其他恶性肿瘤，不包括经过根治的皮肤基底细胞癌、皮肤鳞状细胞癌和/或经过根治切除的原位癌； 2.既往6个月内出现过门静脉高压导致的食管或胃底静脉曲张出血事件。首次给药前3个月内已知的内镜检查存在重度（G3）静脉曲张；有门静脉高压证据（包括影像学检查发现脾大），经研究者评估出血风险高者； 3.既往3个月内发生任何危及生命的出血事件，包括需要输血治疗、手术或局部治疗、持续药物治疗； 4.既往6个月内动、静脉血栓栓塞事件，包括心肌梗死、不稳定型心绞痛、脑血管意外或一过性脑缺血发作、肺动脉栓塞、深静脉血栓或其它任何严重血栓栓塞的病史，植入式静脉输液港或导管源性血栓形成或浅表静脉血栓形成，经过常规抗凝治疗后血栓稳定者除外，允许预防性使用小剂量低分子肝素（如依诺肝素40 mg/天）； 5.首次给药前2周内，连续10天使用阿司匹林（＞ 325 mg/天）或其他已知可以抑制血小板功能的药物如双嘧达莫或氯吡格雷等； 6.不可控制的高血压, 经最佳医学治疗后收缩压＞150mmHg或舒张压＞90 mmHg，高血压危象或高血压脑病病史； 7.症状性充血性心力衰竭（纽约心脏病协会分级II-IV级）。症状性或控制不佳的心律失常。先天性长QT综合征病史或筛查时校正的QTc＞500ms（使用Fridericia法计算）； 8.严重出血倾向或凝血功能障碍，或正在接受溶栓治疗； 9.既往6个月内有胃肠道穿孔和/或瘘管病史，肠梗阻病史（包括需要肠外营养的不完全肠梗阻），广泛肠切除（部分结肠切除或广泛小肠切除，并发慢性腹泻）、克罗恩氏病、溃疡性结肠炎或长期慢性腹泻； 10.筛选入组前24周内接受脑膜瘤放射治疗的患者； 11.既往和目前有肺纤维化史、间质性肺炎、尘肺、药物相关肺炎、肺功能严重受损等肺部疾病； 12.活动性肺结核(TB)，正在接受抗结核治疗或者首次给药前1年内接受过抗结核治疗者； 13.急性或者慢性活动性乙型肝炎或丙型肝炎感染者，乙型肝炎病毒（HBV） DNA＞2000IU/ml或104拷贝/ml；丙型肝炎病毒（HCV）RNA＞103拷贝/ml；乙肝表面抗原（HbsAg）与抗HCV抗体同时阳性； 14.人免疫缺陷病毒（HIV）感染者（HIV 1/2抗体阳性），已知的梅毒感染者； 15.处于活动期或临床控制不佳的严重感染。在首次给药前4周内有重度感染，包括但不限于因感染、菌血症或重度肺炎并发症而住院治疗； 16.首次给药前2年内发生过需要全身性治疗（例如使用缓解疾病药物、皮质类固醇或免疫抑制剂）的活动性自身性免疫疾病。允许使用替代疗法（例如甲状腺素、胰岛素或者用于肾上腺或垂体机能不全的生理性皮质类固醇等）。已知的原发性免疫缺陷病史。仅存在自身免疫抗体阳性的患者需根据研究者判断确认是否存在自身免疫性疾病； 17.首次给药前4周之内使用过免疫抑制药物，不包括喷鼻、吸入性或其他途径的局部糖皮质激素或生理剂量的系统性糖皮质激素（即不超过10mg/天泼尼松或等效剂量的其他糖皮质激素）、允许因治疗哮喘、慢性阻塞性肺疾病等疾病的呼吸困难症状临时使用糖皮质激素； 18.首次给药前4周之内或计划在研究期间接受减毒活疫苗； 19.首次给药前4周之内接受过重大的外科手术（开颅、开胸或开腹手术）或者未愈合的伤口、溃疡或骨折。首次给药之前7天内接受过组织穿刺活检或其他小外科手术，以静脉输液为目的的静脉穿刺置管除外； 20.首次给药前2周内接受过具有抗肿瘤适应症的中药，或接受过具有免疫调节作用的药物（包括胸腺肽、干扰素、白介素，除外为控制胸水或腹水局部使用）； 21.不受控制/无法纠正的代谢紊乱或其它非恶性肿瘤器官疾病或全身性疾病或癌症继发反应，并可导致较高医学风险和/或生存期评价不确定性； 22.既往接受过任何抗PD-1抗体、抗PD-L1/L2抗体、抗CTLA4抗体，或其他免疫治疗。既往接受过抗血管生成靶向治疗； 23.已知对于任何信迪利单抗、仑伐替尼制剂成分过敏，或既往对其他单克隆抗体或酪氨酸激酶抑制剂产生过严重过敏反应； 24.首次给药前4周内接受过其他临床试验的治疗； 25.妊娠或哺乳的女性患者； 26.增加研究参与或研究药物给药的相关风险，或者干扰研究结果的解读，而且根据研究者的判断将患者列为不符合参加本研究的资格。

Exclusion criteria：

1. Diagnosed with other malignancies within 5 years prior to initial administration, excluding radical basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or radical resection of carcinoma in situ; 2. Esophageal or fundus variceal bleeding events caused by portal hypertension have occurred in the past 6 months. Known endoscopic presence of severe (G3) varicose veins within 3 months prior to first dosing; Patients with evidence of portal hypertension (including splenomegaly on imaging) who are at high risk of bleeding as assessed by the investigator; 3. Any life-threatening bleeding event within the previous 3 months, including the need for blood transfusion treatment, surgery or local treatment, continuous medication; 4. Previous arterial or venous thromboembolism events, including myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any other history of severe thromboembolism within the past 6 months, except those with implantable intravenous infusion ports or catheter-borne thrombosis or superficial venous thrombosis, and thromboembolism stabilization after routine anticoagulant therapy, Allow the prophylactic use of low-dose, low-molecular heparin (e.g., enoxaparin 40 mg/ day); 5. Use aspirin (> 325 mg/ day) or other drugs known to inhibit platelet function, such as dipyridamole or clopidogrel, for 10 consecutive days within 2 weeks before the first administration; 6. Uncontrolled hypertension, systolic blood pressure > 150mmHg or diastolic blood pressure > 90 mmHg after optimal medical treatment, history of hypertensive crisis or hypertensive encephalopathy; 7. Symptomatic congestive heart failure (New York Heart Association Grade II-IV). Symptomatic or poorly controlled arrhythmia. A QTc > 500ms adjusted for congenital long QT syndrome history or screening (calculated using the Fridericia method); 8. Severe bleeding tendency or coagulation dysfunction, or receiving thrombolytic therapy; 9. A previous history of gastrointestinal perforation and/or fistula within the last 6 months, a history of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive enterectomy (partial colectomy or extensive enterectomy with chronic diarrhea), Crohn's disease, ulcerative colitis, or long-term chronic diarrhea; 10. Screening patients who received radiation therapy for meningioma within the first 24 weeks of enrollment; 11. Previous or current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-related pneumonia, severe impairment of lung function, and other lung diseases; 12. People with active tuberculosis (TB) who are receiving anti-TB therapy or who have received anti-TB therapy within 1 year prior to the first dose; 13. Persons infected with acute or chronic active hepatitis B or hepatitis C, hepatitis B virus (HBV) DNA > 2000IU/ml or 104 copies /ml; Hepatitis C virus (HCV) RNA > 103 copies /ml; Hepatitis B surface antigen (HbsAg) and anti-HCV antibody were positive simultaneously; 14. Human immunodeficiency virus (HIV) infection (HIV 1/2 antibody positive), known syphilis infection; 15. A serious infection that is active or poorly controlled clinically. Severe infection in the 4 weeks prior to initial dosing, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia; 16. An active autoimmune disease requiring systemic treatment (e.g. with disease-modifying drugs, corticosteroids, or immunosuppressants) occurred within 2 years prior to first administration. Alternative therapies (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are permitted. Known history of primary immunodeficiency. Only patients with positive autoimmune antibodies should be confirmed whether there is an autoimmune disease according to the judgment of the investigator; 17. Use of immunosuppressive drugs within 4 weeks prior to the first dose, Does not include nasal, inhaled, or other routes of topical corticosteroids or physiological doses of systemic corticosteroids (i.e., not more than 10mg/ day of prednisone or equivalent doses of other corticosteroids), allowing temporary use of corticosteroids for the treatment of respiratory difficulties in asthma, chronic obstructive pulmonary disease and other diseases; 18. Receive live attenuated vaccine within 4 weeks prior to initial administration or during the study period; 19. Major surgical procedures (craniotomy, thoracotomy, or laparotomy) or unhealed wounds, ulcers, or fractures within 4 weeks prior to initial dosing. Have undergone tissue biopsy or other minor surgical procedures within 7 days prior to initial administration, except for venipuncture for intravenous infusion; 20. Received Chinese medicines with anti-tumor indications or immunomodulatory effects (including thymosin, interferon, and interleukin, except for local use to control pleural fluid or ascites) within 2 weeks prior to initial administration; 21. Uncontrolled/uncorrectable metabolic disorders or other non-malignant organ disease or systemic disease or cancer secondary reactions that can lead to higher medical risk and/or uncertainty in the evaluation of survival; 22.Any previous anti-PD-1 antibody, anti-PD-L1 /L2 antibody, anti-CTLA4 antibody, or other immunotherapy. Previously received anti-angiogenesis targeted therapy; 23. Is known to be allergic to any Sintilimab, or Lenvatinib formulation ingredient, or has had a previous severe allergic reaction to other monoclonal antibodies or tyrosine kinase inhibitors; 24. Received treatment in other clinical trials within 4 weeks prior to initial dosing; 25. Pregnant or nursing female patients. 26. Increase the risk of research participation or drug administration, or interfere with the interpretation of research results, and classify patients as ineligible to participate in this study based on the researcher's judgment.

研究实施时间：

Study execute time：

从 From 2023-09-01 00:00:00至 To 2026-09-30 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2023-12-20 00:00:00 至 To 2024-09-30 00:00:00  

干预措施：

Interventions：

组别：

实验组

样本量：

25

Group：

Experimental group

Sample size：

干预措施：

信迪利单抗联合仑伐替尼

干预措施代码：

Intervention：

Sintilimab Combined with Lenvatinib

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 辽宁 

市(区县)：

 沈阳 

Country：

China 

Province：

Liaoning 

City：

Shenyang 

单位(医院)：

中国人民解放军北部战区总医院 

单位级别：

三甲 

Institution
hospital：

General Hospital of the Northern Theater Command of the Chinese People's Liberation Army

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

6个月PFS率

指标类型：

主要指标

Outcome：

6-month PFS 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：

无进展生存

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

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：

客观缓解率

指标类型：

次要指标

Outcome：

objective 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：

疾病控制率

指标类型：

次要指标

Outcome：

disease control 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：

缓解持续时间

指标类型：

次要指标

Outcome：

Duration of relief

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：

次要指标

Outcome：

safety

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：

组织

组织：

Sample Name：

Tissue

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）：

不适用

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

N/A

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）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

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）：

未说明

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

Not stated

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：

CRF

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：

  2023-12-20 16:28:30