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Phase Ib study to evaluate the safety, feasibility and efficacy of KL-A167 monotherapy in neoadjuvant/adjuvant therapy for resectable lung squamous cell carcinoma.
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注册号:

Registration number:

ChiCTR1900023375 

最近更新日期:

Date of Last Refreshed on:

2019-05-25 

注册时间:

Date of Registration:

2019-05-25 

注册号状态:

预注册  

Registration Status:

Prospective registration  

注册题目:

评估KL-A167单药用于可切除肺鳞癌新辅助/辅助治疗的安全性、可行性和有效性Ⅰb期研究 

Public title:

Phase Ib study to evaluate the safety, feasibility and efficacy of KL-A167 monotherapy in neoadjuvant/adjuvant therapy for resectable lung squamous cell carcinoma. 

注册题目简写:

 

English Acronym:

 

研究课题的正式科学名称:

评估KL-A167单药用于可切除肺鳞癌新辅助/辅助治疗的安全性、可行性和有效性Ⅰb期研究 

Scientific title:

Phase Ib study to evaluate the safety, feasibility and efficacy of KL-A167 monotherapy in neoadjuvant/adjuvant therapy for resectable lung squamous cell carcinoma. 

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:

张帆 

研究负责人:

高树庚 

Applicant:

Fan Zhang 

Study leader:

Shugeng Gao 

申请注册联系人电话:

Applicant telephone:

+86 18911223795 

研究负责人电话:

Study leader's telephone:

+86 13801185056 

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:

timzhang8702@163.com 

研究负责人电子邮件:

Study leader's E-mail:

gaoshugeng@vip.sina.com 

申请单位网址(自愿提供):

Applicant website(voluntary supply):

http://www.cicams.ac.cn 

研究负责人网址(自愿提供):

Study leader's website(voluntary supply):

http://www.cicams.ac.cn 

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:

17 Panjiayuan Street South, Chaoyang District, Beijing 

Study leader's address:

17 Panjiayuan Street South, Chaoyang District, Beijing 

申请注册联系人邮政编码:

Applicant postcode:

100021 

研究负责人邮政编码:

Study leader's postcode:

100021 

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 

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:

18-166/1745 

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 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:

2018-09-13 

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:

17 Panjiayuan Street South, Chaoyang District, Beijing 

伦理委员会联系人电话:

Contact phone of the ethic committee:

+86 010-87788495 

伦理委员会联系人邮箱:

Contact email of the ethic committee:

N/A 

研究实施负责(组长)单位:

中国医学科学院北京协和医学院肿瘤医院 

Primary sponsor:

Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College 

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:

17 Panjiayuan Street South, Chaoyang District, Beijing 

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):

朝阳区

Country:

China

Province:

Beijing

City:

Chaoyang District

单位(医院):

中国医学科学院北京协和医学院肿瘤医院

具体地址:

潘家园南里17号

Institution
hospital:

Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Address:

17 Panjiayuan Street South

经费或物资来源:

该研究项目所需资源,大部分由申办方自筹,试验药物和部分经费来自于四川科伦博泰生物医药股份有限公司赞助。 

Source(s) of funding:

Most of the resources needed for the research project are self-raised by the sponsor, and the experimental drugs and some funds are sponsored by sichuan kelunbotai bio-pharmaceutical co., LTD 

研究疾病:

肺鳞癌 

Target disease:

lung squamous cell carcinoma 

研究疾病代码:

N/A 

Target disease code:

N/A 

研究类型:

观察性研究 

Study type:

Observational study 

研究所处阶段:

I期临床试验 

Study phase:

研究目的:

主要目的: 1.评估KL-A167单药用于可切除肺鳞癌患者新辅助治疗中的安全性、可行性和耐受性; 2.评估KL-A167单药用于可切除肺鳞癌新辅助和辅助治疗后的无疾病生存期(disease free survival, DFS),最长观察时间2年。 

Objectives of Study:

The main objectives are: 1. To evaluate the safety, feasibility and tolerance of KL-A167 monotherapy in neoadjuvant therapy for resectable lung squamous cell carcinoma. 2. To evaluate the disease-free survival (DFS) of KL-A167 monotherapy after neoadjuvant and adjuvant therapy for resectable lung squamous cell carcinoma, with a maximum duration of 2 years. 

药物成份或治疗方案详述:

KL-A167为重组抗PD-L1人源化单克隆抗体,本研究是评估KL-A167单药用于可切除肺鳞癌新辅助/辅助治疗的安全性、可行性和有效性Ⅰb期研究。 本研究分为两个阶段:第一阶段为安全性导入研究,先纳入6例患者,采用单中心设计;如果没有出现主要安全性事件,则进入第二阶段,继续纳入24例患者,总共扩展至30例患者,采用多中心设计。 未经任何治疗的可手术的肺鳞癌患者,签署知情同意后,经筛选符合入排标准,接受KL-A167 900mg iv Q2W治疗3周期(1周期为14天)后,并在距离首次KL-A167治疗36~43天内,接受肺鳞癌根治性手术治疗及术后辅助治疗。术后选择使用KL-A167辅助治疗或标准辅助治疗的方式和疗程由研究者决定。待完成3~6例受试者的治疗和安全性评估后,再决定是否开展1500mg扩展研究。 本研究采用RECIST V1.1进行影像学评估,在基线和术前(第3次KL-A167给药后、术前1周内)进行PET-CT和增强CT检查;术后第30天、辅助KL-A167治疗结束时及术后每3个月进行增强CT检查及疗效评价,直到术后2年、疾病复发或死亡。筛选期需要行增强CT排除脑转移。 研究过程中,受试者将接受安全性随访(KL-A167末次用药后90天或术后30天,以后发生者为准)以及术后无复发生存随访(每90±7天,直到术后2年)。 

Description for medicine or protocol of treatment in detail:

 

研究设计:

单臂 

Study design:

Single arm 

纳入标准:

1. 细胞学或组织学诊断为肺鳞状细胞癌; 2. 同意采集本研究需要的肿瘤组织学标本并应用于相关研究; 3. 未经任何治疗、可手术切除的肺鳞状细胞癌,肿瘤直径必须≥2cm; 4. 同意接受根治性手术治疗的患者; 5. 胸外科医师判断无手术禁忌的患者; 6. 至少有一个可测量病灶(RECIST V1.1); 7. 男或女性≥18周岁,且≤75周岁; 8. ECOG评分为0; 9. 重要器官和骨髓功能符合以下要求: a) 血常规:中性粒细胞绝对计数(ANC)≥1.5×10^9/L,血小板(PLT)≥100×10^9/L,血红蛋白(HGB)≥9g/dL; b) 肝功能:血清总胆红素(TBIL)≤1.5倍正常上限(ULN),丙氨酸氨基转移酶(ALT)和/或天门冬氨酸氨基转移酶(AST)≤2.5倍ULN,血清白蛋白(ALB)≥2.8g/dL; c) 肾功能:血清肌酐(Cr)≤1.5×ULN,或肌酐清除率≥40ml/min(应用标准的Cockcroft-Gault公式,详见附件4); 10. 育龄期女性受试者或性伴侣为育龄期女性的男性受试者,需在整个治疗期及最后一次治疗后90天内采取有效的避孕措施(具体避孕措施见附件5); 11. 签署书面知情同意书,并且能够遵守方案规定的访视及相关程序。 

Inclusion criteria

1. Cytological or histological diagnosis of lung squamous cell carcinoma; 2. Agree to collect the histological specimens of tumors needed in this study and apply them to relevant research; 3. Untreated and resectable squamous cell carcinoma of the lung must have a diameter greater than or equal to 2 cm. 4. Patients who agree to receive radical surgery; 5. Thoracic surgeons judge patients without surgical contraindications. 6. At least one measurable lesion (RECIST V1.1); 7. Male or female (≥18 years old) and (≤75 years old); 8. ECOG score was 0. 9. Important organs and bone marrow functions meet the following requirements: (a) Blood routine: absolute neutrophil count (ANC)≥ 1.5 *10^9/L, platelet (PLT) ≥ 100 *10^9/L, hemoglobin (HGB) ≥ 9g/dL; (b) Liver function: serum total bilirubin (TBIL) = 1.5 times normal upper limit (ULN), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) = 2.5 times ULN, serum albumin (ALB) ≥2.8 g/dL; C) Renal function: serum creatinine (Cr) is less than 1.5 x ULN, or creatinine clearance rate is more than 40 ml/min (using standard Cockcroft-Gault formula, see Annex 4 for details); 10. Female subjects of childbearing age or male subjects whose sexual partners are women of childbearing age should take effective contraceptive measures during the whole treatment period and within 90 days after the last treatment (see Annex 5 for specific contraceptive measures). 11. Sign a written informed consent and be able to comply with the programme's visits and related procedures. 

排除标准:

1. 既往曾接受过任何抗肿瘤治疗,包括放疗、化疗、免疫治疗及中药治疗(既往根治且无复发转移时间≥5年的恶性肿瘤的治疗除外); 2. 在首剂研究治疗之前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); 3. 已知或怀疑活动性自身免疫性疾病(先天性或获得性),如间质性肺炎、葡萄膜炎、肠炎、肝炎、垂体炎、血管炎、肾炎、甲状腺炎等(白癜风或在童年期哮喘已完全缓解,成人后无需任何干预的患者可以入组;胰岛素控制良好的I型糖尿病患者也可以入组); 4. 已知异体器官移植(角膜移植除外)或异体造血干细胞移植; 5. 对单克隆抗体任何成分过敏; 6. 现患有间质性肺病; 7. 患有其他未控制的严重疾病,包括但不限于: 1) 处于活动期或临床控制不佳的严重感染; 2) HIV感染者(HIV抗体阳性); 3) 患有急性或慢性活动性乙型肝炎(HBsAg阳性且HBV DNA>1*10^3/ml)或急性或慢性活动性丙型肝炎(HCV抗体阳性且HCV RNA检测阳性); 4) 活动性肺结核等; 5) III-IV级充血性心力衰竭(纽约心脏病协会分级),控制不佳且有临床意义的心律失常; 6) 未能控制的动脉高血压(收缩压≥160mmHg或舒张压≥100mmHg); 7) 在入选治疗前6个月内发生过任何动脉血栓、栓塞或缺血,如心肌梗死、不稳定型心绞痛、脑血管意外或一过性脑缺血发作; 8) 需要使用华法林(香豆素)抗凝治疗的疾病; 9) 未控制的高钙血症(大于1.5mmol/L钙离子或钙大于12mg/dL或校正后血清钙大于ULN),或需要继续接受双磷酸盐治疗的症状性高钙血症; 10) 同时伴有其他的恶性肿瘤(已根治的除外,如子宫颈原位癌,非黑色素瘤皮肤癌等); 8. 可能会导致以下结果的其它急性或慢性疾病、精神疾病或实验室检测值异常:增加参与研究或研究药物给药的相关风险,或者干扰研究结果的解读,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; 9. 妊娠或哺乳期女性。 

Exclusion criteria:

1. Previous anti-cancer treatments, including radiotherapy, chemotherapy, immunotherapy and traditional Chinese medicine (except for malignant tumors which had been radically cured and had no recurrence or metastasis for more than 5 years); 2. Immunosuppressive drugs were used within 4 weeks prior to the first dose of the study, excluding local glucocorticoids or systemic glucocorticoids (i.e. no more than 10 mg/prednisone or other glucocorticoids of equivalent dose) through nasal spray, inhalation or other routes. 3. Known or suspected active autoimmune diseases (congenital or acquired), such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, thyroiditis, etc. (Vitiligo or childhood asthma has been completely alleviated, adults without any intervention can be enrolled in the group; Type I diabetes patients with good insulin control can also be enrolled in the group); 4. Known allograft organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation; 5. Allergy to any component of monoclonal antibody; 6. He/she is suffering from interstitial lung disease; 7. To suffer from other serious uncontrolled diseases, including but not limited to: 1) Severe infections at active stage or under clinical control; 2) HIV infected persons (HIV antibody positive); 3) Patients with acute or chronic active hepatitis B (HBsAg positive and HBV DNA > 1*10^3/ml) or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA positive); 4) Active pulmonary tuberculosis, etc. 5) Class III-IV congestive heart failure (New York Heart Association Classification), poorly controlled and clinically significant arrhythmias; 6) Uncontrolled arterial hypertension (systolic pressure (≥160 mmHg) or diastolic pressure (≥ 100 mmHg); 7) Any arterial thrombosis, embolism or ischemia, such as myocardial infarction, unstable angina pectoris, cerebrovascular accident or transient ischemic attack, occurred within 6 months before admission. 8) Diseases requiring anticoagulant therapy with warfarin (coumarin); 9) Uncontrolled hypercalcemia (more than 1.5mmol/L of calcium or more than 12mg/dL of calcium or more than ULN of serum after correction), or symptomatic hypercalcemia requiring continued bisphosphate therapy; 10) It is accompanied by other malignant tumors (except those cured, such as cervical carcinoma in situ, non-melanoma skin cancer, etc.). 8. Other acute or chronic diseases, psychiatric disorders or abnormal laboratory test values that may lead to the following results: increasing the risk associated with participating in research or drug administration, or interfering with the interpretation of research results, and classifying patients as not eligible to participate in this study according to the judgement of researchers; 9. Pregnant or lactating women. 

研究实施时间:

Study execute time:

From2019-05-01To 2020-12-31 

征募观察对象时间:

Recruiting time:

From2019-06-15To 2020-02-29 

干预措施:

Interventions:

组别:

1

样本量:

30

Group:

1

Sample size:

干预措施:

KL-A167

干预措施代码:

Intervention:

KL-A167

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 

市(区县):

朝阳区 

Country:

China 

Province:

Beijing 

City:

Chaoyang District 

单位(医院):

中国医学科学院北京协和医学院肿瘤医院 

单位级别:

潘家园南里17号 

Institution
hospital:

Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  

Level of the institution:

7 Panjiayuan Street South 

测量指标:

Outcomes:

指标中文名:

无疾病生存期(DFS)

指标类型:

主要指标 

Outcome:

disease free survival (DFS)

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:

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:

1年和2年疾病复发的患者比例

指标类型:

次要指标 

Outcome:

RR

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:

OS

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

主要病理学缓解率

指标类型:

次要指标 

Outcome:

MPR

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

使用后保存 

说明

保存至试验结束后2年

Fate of sample:

Preservation after use 

Note:

Preserved until 2 years after the end of the experiment

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:

新鲜肿瘤组织样本

组织:

Sample Name:

Fresh Tumor Tissue Samples

Tissue:

lung

人体标本去向

使用后保存 

说明

长期保存

Fate of sample:

Preservation after use 

Note:

Long term preservation

征募研究对象情况:

Recruiting status:

尚未开始

Not yet recruiting

年龄范围:

Participant age:

最小 Min age 18 years
最大 Max age 75 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):

无随机,单臂试验

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

Random-free single arm trial.

盲法:

N/A

Blinding:

N/A

原始数据公开时间:

The time of sharing IPD:

Within six months after the trial complete

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):

试验完成半年后,相应原始数据将会参照ICMJE(International Committee of Medical Journal Editors)的要求在适当的平台对外公开,预计公开日期为2021年7月,具体时间视实际试验完成时间而定。

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

Half a year after the completion of the experiment, the corresponding raw data will be published on the appropriate platform in accordance with the requirements of ICMJE (International Committee of Me

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:

本研究前6例患者建议采用手工操作记录进行数据管理。若后续病例扩展至30例,后续24例患者采用电子数据采集(EDC)系统进行数据管理,研究数据将由研究者或授权的研究人员录入到eCRF中。研究中心启动或数据录入前,将对研究者和授权的研究人员进行适当培训,并对所使用的电脑等设备采取适当的安全措施。

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture:

The first six patients in this study recommended manual operation records for data management. If the following cases were extended to 30 cases, the data of 24 cases were managed by EDC(Electronic Data Capture) system, and the research data would be input into eCRF by researchers or authorized researchers. Researchers and authorized researchers will be properly trained and appropriate security measures will be taken for the computer and other equipment used before the research center starts or data entry.

数据管理委员会:

Data Managemen Committee:

有/Yes

注册人:

Name of Registration:

 2019-05-25
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