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招募患者:Nivolumab注射液治疗晚期或转移性非小细胞肺癌的临床试验

2015-12-27 MedSci MedSci原创

一、题目和背景信息  登记号: CTR20150767  适应症: 晚期或转移性非小细胞肺癌  试验通俗题目: 对复发的晚期或转移性非小细胞肺癌的研究  试验专业

一、题目和背景信息

 登记号: CTR20150767
 适应症: 晚期或转移性非小细胞肺癌
 试验通俗题目: 对复发的晚期或转移性非小细胞肺癌的研究
 试验专业题目: Nivolumab对比多西他赛治疗既往接受过治疗的晚期或转移性非小细胞肺癌的开放性、随机、多个国家参加的III期试验
 试验方案编号: CA209-078
 临床申请受理号: JXSL1300032
 药物名称: Nivolumab注射液
 药物类型: 生物制品

     二、申办者信息

 申办者名称:
1 Bristol-Myers Squibb Company/Bristol-Myers Squibb Company
2 Bristol-Myers Squibb Holdings Pharma, Ltd/Bristol-Myers Squibb Holdings Pharma, Ltd
3 百时美施贵宝(中国)投资有限公司/
 联系人姓名: 刘蔚
 联系人电话: 021-23218416  联系人Email: kelly.liu@bms.com
 联系人邮政地址: 上海市南京西路1717号会德丰广场15楼  联系人邮编: 200040
 试验项目经费来源: 完全自筹

     三、临床试验信息

 1、试验目的
在以前用含铂剂化疗失败的晚期或转移性NSCLC受试者中,比较nivolumab组与多西他赛组的总生存期,客观缓解率和无进展生存期。评价nivolumab组与多西他赛组重度不良事件(3级和4级)的发生率。根据肺癌症状量表评价结果,评价nivolumab组与多西他赛组到12周时疾病相关症状有改善的受试者所占的比例。
 2、试验设计(单选)
试验分类: 安全性和有效性
试验分期: III期
设计类型: 平行分组
随机化: 随机化
盲法: 开放
试验范围: 国际多中心试验
 3、受试者信息
年龄   18岁(最小年龄)至 无岁(最大年龄)
性别   男+女
健康受试者   无
入选标准
1 组织学或细胞学确诊为NSCLC、并且有IIIB期/IV期肿瘤(按照国际肺癌研究协会胸部肿瘤分期手册(International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology)第7版判断)或多模式治疗(放疗、手术切除或根治性放化疗治疗局部晚期疾病)后复发或疾病进展的受试者。
2 受试者必须在以前用一种含铂剂二联化疗方案治疗晚期或转移性肿瘤期间或以后发生了疾病进展。 ? 接受维持治疗(是指用含铂剂二联化疗方案后无进展者接受的治疗)并发生了进展的受试者适合入选。 ? 使用含铂的辅助、新辅助治疗或根治性放化疗治疗局部晚期疾病、并且在完成治疗后6个月内发生了肿瘤复发或转移的受试者适合入选。 ? 给予含铂的辅助、新辅助治疗或根治性放化疗治疗局部晚期疾病后>6个月以后肿瘤复发、并且后来在用铂剂二联方案治疗复发性肿瘤期间或以后又发生了进展的受试者适合入选。
3 按照RECIST 1.1标准(附录2),受试者必须有通过CT或MRI检查的可测量病变。肿瘤影像学评价在随机分组之前的28天内进行。 a) 目标病灶可以位于以前放疗过的区域,只要证实(影像学检查)该部位有疾病进展。
4 ≥18岁的男性和女性
5 ECOG体力状况评分≤1
6 必须有一份经福尔马林固定、石蜡包埋(FFPE)的肿瘤组织块或至少10张未染色的肿瘤标本切片(如果BMS医学监查员批准,可提交不到10张未染色切片)必须在中心实验室进行生物标志物评价(肿瘤标本可以是存档或近期的标本)。为了进行随机,将受试者分为PD-L1阳性、PD-L1阴性或PD-L1无法评估。活检标本应该是切除的标本、切取的标本或空心针穿刺标本。细针穿刺活检的标本、胸腔积液引流离心的细胞涂片、或者钻取活检不足以用于生物标志物的审阅和随机化。没有软组织成分或脱钙骨肿瘤标本的骨病变也不可接受。
7 随机分组之前,以前对非CNS病变进行的姑息放疗必须已经完成至少2周。强烈建议,在基线期存在有症状的肿瘤病灶且可能需要在随机分组后4周内进行姑息放疗的受试者,在随机分组之前接受姑息放疗。
排除标准
1 受试者有癌性脑膜炎。
2 要排除有活动性中枢神经系统(CNS)转移的受试者。如果受试者的CNS转移能够充分治疗,并且受试者的神经系统症状能够在入选前至少2周恢复到基线水平(与CNS治疗有关的残留体征或症状除外),则可以参加研究。此外,受试者还必须是不用皮质类固醇的受试者,或接受剂量稳定或逐渐降低的≤10mg/天的强的松(或等价物)。
3 排除患有活动性、已知或可疑的自身免疫性疾病的受试者。患有I型糖尿病、只需接受激素替代治疗的甲状腺功能减退症、无需进行全身治疗的皮肤疾病(例如,白癜风、银屑病或脱发),或预计在无外部触发因素的状态下情况不会再现的受试者可以入选。
4 随机分组之前的14天内有需要全身用皮质类固醇(剂量相当于>10 mg强的松/天)或其他免疫抑制药物治疗的受试者。使用吸入性或外用皮质类固醇的受试者,以及肾上腺皮质类固醇替代治疗剂量相当于>10 mg强的松/天的受试者,如果没有活动性自身免疫性疾病,则可以参加研究。
5 以前用过抗肿瘤疫苗或其他具有免疫刺激作用的抗肿瘤药治疗。
6 以前用过抗PD-1抗体、抗PD-L1抗体、抗PD-L2抗体、抗CD137抗体或抗CTLA-4抗体治疗(包括ipilimumab或特异性作用于T细胞协同刺激或检查点途径的任何其他抗体或药物)。
7 以前用过多西他赛治疗。
8 乙型肝炎病毒表面抗原(HBV sAg)或丙型肝炎病毒抗体(HCV Ab)阳性,说明有急性或慢性感染。
9 根据胸部X线检查、痰液检查以及临床查体,判断有活动性肺结核(TB)感染。前1年内有活动性肺结核感染病史的患者,即使已经治疗,也要排除;超过1年以前有活动性肺结核感染病史的患者,也要排除,除非证明以前所用的抗结核治疗的疗程和种类都恰当。
10 排除EGFR突变的受试者(不考虑突变类型)。必须对EGFR突变状态未知的非鳞癌受试者的EGFR突变状态进行检测(强烈建议采用基于PCR的检测方法)。如果EGFR突变为阳性,则排除受试者。
11 排除已知ALK易位的受试者。
12 既往在伊匹木单抗一线NSCLC研究CA184153中接受过盲态研究药物治疗(无论哪个治疗组)的受试者。在开放期前接受安慰剂治疗的患者可以入选。
目标入组人数   国际多中心试验:总体500人, 中国450人;
实际入组人数   登记人暂未填写该信息
 4、试验分组
试验药
序号 名称 用法
1 Nivolumab 注射液 注射液;规格100 mg (10 mg/mL)/瓶,3mg/kg,每个治疗周期的第1天(每2周1个周期)静脉输注,每次输注60分钟。用药时程:连续给药直至疾病进展或发生不可接受的毒性。
对照药
序号 名称 用法
1 多西他赛注射液 注射液;规格20 mg (1.5 ml/瓶),75mg/m2,在每个治疗周期的第1天(每3周1个周期)静脉输注,每次输注60分钟,每次输注60分钟。用药时程:连续给药直至疾病进展或发生不可接受的毒性。
 5、终点指标
主要终点指标及评价时间
序号 指标 评价时间 终点指标选择
1 总生存期(评价Nivolumb 在晚期或转移性非小细胞肺癌患者的总生存期) 总生存期的中期分析将在第一例患者第一次访视后的27个月进行。 如果研究在中期分析时未中止,那么最终的总生存期分析将会在第一例患者第一次访视后的37个月进行。 有效性指标
次要终点指标及评价时间
序号 指标 评价时间 终点指标选择
1 按照RECIST 1.1标准评定客观缓解率 生存期完成时进行分析 有效性指标
2 按照RECIST 1.1标准评定无进展生存期 生存期完成时进行分析 有效性指标
3 评价不同亚组的临床疗效(总生存期、客观缓解率和无进展生存期) 生存期完成时进行分析 有效性指标
4 重度不良事件(3级和4级)的发生率 生存期完成时进行分析 安全性指标
5 根据肺癌症状量表评价结果,评价到12周时疾病相关症状有改善的受试者所占的比例 生存期完成时进行分析 安全性指标
 6、数据安全监察委员会(DMC):    有
 7、为受试者购买试验伤害保险:   有

     四、第一例受试者入组日期

登记人暂未填写该信息
登记人暂未填写该信息

     五、试验终止日期

登记人暂未填写该信息
登记人暂未填写该信息

     六、研究者信息

1、主要研究者信息
姓名 程颖 职称 主任医师
电话 0431-85871902 Email jl.cheng@163.com
邮政地址 吉林省长春市湖光路1018号 邮编 130012
单位名称 吉林省肿瘤医院
2、各参加机构信息
序号 机构名称 主要研究者 国家 省(州) 城市
1 吉林省肿瘤医院 程颖 中国 吉林 长春
2 National University Hospital Singapore Chee Seng Tan Singapore Singapore Singapore

     七、伦理委员会信息

序号 名称 审查结论 审查日期
1 吉林省肿瘤医院伦理委员会 同意 2015-10-21

     八、试验状态

进行中 (尚未招募)

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  1. 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topicName=转移性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1ac22500003, createdName=1249842em09(暂无昵称), createdTime=Tue Dec 29 05:04:00 CST 2015, time=2015-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1471993, encodeId=876414e1993f6, content=<a href='/topic/show?id=c4d79344044' target=_blank style='color:#2F92EE;'>#转移性非小细胞肺癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93440, encryptionId=c4d79344044, topicName=转移性非小细胞肺癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=14b77195705, createdName=anan, createdTime=Tue Dec 29 05:04:00 CST 2015, time=2015-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1548494, encodeId=dd051548494d7, content=<a href='/topic/show?id=6a4756229d9' target=_blank style='color:#2F92EE;'>#招募#</a>, beContent=null, objectType=article, channel=null, 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    2016-09-30 tamgche
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topicName=转移性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1ac22500003, createdName=1249842em09(暂无昵称), createdTime=Tue Dec 29 05:04:00 CST 2015, time=2015-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1471993, encodeId=876414e1993f6, content=<a href='/topic/show?id=c4d79344044' target=_blank style='color:#2F92EE;'>#转移性非小细胞肺癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93440, encryptionId=c4d79344044, topicName=转移性非小细胞肺癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=14b77195705, createdName=anan, createdTime=Tue Dec 29 05:04:00 CST 2015, time=2015-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1548494, encodeId=dd051548494d7, content=<a href='/topic/show?id=6a4756229d9' target=_blank style='color:#2F92EE;'>#招募#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56229, encryptionId=6a4756229d9, topicName=招募)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=038c14086626, createdName=ms1260584454294838, createdTime=Tue Dec 29 05:04:00 CST 2015, time=2015-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1586514, encodeId=6eb8158651439, content=<a href='/topic/show?id=f87c6499085' target=_blank style='color:#2F92EE;'>#注射液#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64990, encryptionId=f87c6499085, topicName=注射液)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c93417353045, createdName=shijzhiewnjhch, createdTime=Tue Dec 29 05:04:00 CST 2015, time=2015-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=49842, encodeId=e15649842f0, content=赞, 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  3. [GetPortalCommentsPageByObjectIdResponse(id=2007854, encodeId=c32e200e854b1, content=<a href='/topic/show?id=601512826f6' target=_blank style='color:#2F92EE;'>#NIV#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12826, encryptionId=601512826f6, topicName=NIV)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=674961, createdName=tamgche, createdTime=Fri Sep 30 18:04:00 CST 2016, time=2016-09-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2059523, encodeId=c55020595235b, content=<a href='/topic/show?id=2cc599381bd' target=_blank style='color:#2F92EE;'>#非小细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99381, encryptionId=2cc599381bd, topicName=非小细胞)], attachment=null, authenticateStatus=null, createdAvatar=, 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topicName=转移性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1ac22500003, createdName=1249842em09(暂无昵称), createdTime=Tue Dec 29 05:04:00 CST 2015, time=2015-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1471993, encodeId=876414e1993f6, content=<a href='/topic/show?id=c4d79344044' target=_blank style='color:#2F92EE;'>#转移性非小细胞肺癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93440, encryptionId=c4d79344044, topicName=转移性非小细胞肺癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=14b77195705, createdName=anan, createdTime=Tue Dec 29 05:04:00 CST 2015, time=2015-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1548494, encodeId=dd051548494d7, content=<a href='/topic/show?id=6a4756229d9' target=_blank style='color:#2F92EE;'>#招募#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56229, encryptionId=6a4756229d9, topicName=招募)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=038c14086626, createdName=ms1260584454294838, createdTime=Tue Dec 29 05:04:00 CST 2015, time=2015-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1586514, encodeId=6eb8158651439, content=<a href='/topic/show?id=f87c6499085' target=_blank style='color:#2F92EE;'>#注射液#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64990, encryptionId=f87c6499085, topicName=注射液)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c93417353045, createdName=shijzhiewnjhch, createdTime=Tue Dec 29 05:04:00 CST 2015, time=2015-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=49842, encodeId=e15649842f0, content=赞, beContent=null, objectType=article, channel=null, level=null, likeNumber=174, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7cde98330, createdName=milkshark, createdTime=Mon Dec 28 07:04:00 CST 2015, time=2015-12-28, status=1, ipAttribution=)]
    2016-06-03 snf701207
  4. [GetPortalCommentsPageByObjectIdResponse(id=2007854, encodeId=c32e200e854b1, content=<a href='/topic/show?id=601512826f6' target=_blank style='color:#2F92EE;'>#NIV#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12826, encryptionId=601512826f6, topicName=NIV)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=674961, createdName=tamgche, createdTime=Fri Sep 30 18:04:00 CST 2016, time=2016-09-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2059523, encodeId=c55020595235b, content=<a href='/topic/show?id=2cc599381bd' target=_blank style='color:#2F92EE;'>#非小细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99381, encryptionId=2cc599381bd, topicName=非小细胞)], attachment=null, authenticateStatus=null, createdAvatar=, 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level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56229, encryptionId=6a4756229d9, topicName=招募)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=038c14086626, createdName=ms1260584454294838, createdTime=Tue Dec 29 05:04:00 CST 2015, time=2015-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1586514, encodeId=6eb8158651439, content=<a href='/topic/show?id=f87c6499085' target=_blank style='color:#2F92EE;'>#注射液#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64990, encryptionId=f87c6499085, topicName=注射液)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c93417353045, createdName=shijzhiewnjhch, createdTime=Tue Dec 29 05:04:00 CST 2015, time=2015-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=49842, encodeId=e15649842f0, content=赞, beContent=null, objectType=article, channel=null, level=null, likeNumber=174, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7cde98330, createdName=milkshark, createdTime=Mon Dec 28 07:04:00 CST 2015, time=2015-12-28, status=1, ipAttribution=)]
    2016-01-13 Lynee劲飞扬

    0

  5. 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beContent=null, objectType=article, channel=null, level=null, likeNumber=174, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7cde98330, createdName=milkshark, createdTime=Mon Dec 28 07:04:00 CST 2015, time=2015-12-28, status=1, ipAttribution=)]
    2016-01-12 huangshang9812

    恩,以后希望都一点这样的研究

    0

  6. 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  7. 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  8. 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  9. 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  10. 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createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160113/IMG569619FEB03536446.jpg, createdBy=85f81678980, createdName=Lynee劲飞扬, createdTime=Wed Jan 13 17:24:00 CST 2016, time=2016-01-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=56449, encodeId=6f9c564499c, content=恩,以后希望都一点这样的研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=174, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e1ee1608797, createdName=huangshang9812, createdTime=Tue Jan 12 20:03:00 CST 2016, time=2016-01-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1386180, encodeId=2acf1386180e1, content=<a href='/topic/show?id=f08293399f9' target=_blank style='color:#2F92EE;'>#转移性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93399, encryptionId=f08293399f9, 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    2015-12-28 milkshark

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