新辅助曲妥珠单抗+多西紫杉醇+NPLD+/-贝伐珠单抗在 Her2-pos 中的 II 期研究。早期乳腺癌 (ABCSG 32)
2014年5月12日 更新者：Austrian Breast & Colorectal Cancer Study Group
新辅助曲妥珠单抗加多西他赛联合和不联合贝伐单抗以及曲妥珠单抗联合多西他赛联合非聚乙二醇化脂质体包封多柔比星 (NPLD) 联合和不联合贝伐单抗治疗 HER2 阳性早期乳腺癌的多中心随机 II 期研究
HER2 阳性早期乳腺癌新辅助治疗的多中心随机 II 期研究。
主要目的是评估联合治疗（曲妥珠单抗、多西紫杉醇、贝伐珠单抗、NPLD）与标准疗法相比的心脏毒性。
研究概览
地位
完全的
条件
详细说明
目标研究人群包括男性和女性绝经前和绝经后 HER2 阳性乳腺癌（炎症性乳腺癌除外，T4d）计划接受新辅助细胞毒性治疗。
患者必须患有经病理证实的乳腺癌且经组织学证实为 HER2 过度表达。 筛选时，患者必须有足够的左心室射血分数 (LVEF)； ECOG 体能状态为 0 或 1；足够的肝、肾和骨髓功能；并且没有可能影响协议依从性或结果解释的其他严重疾病。
患者不应增加胃肠道穿孔、高血压、蛋白尿、伤口愈合并发症、血栓栓塞或出血的风险。 患者不得患有可能影响方案依从性或结果解释的其他原发性恶性肿瘤。 患有中枢神经系统 (CNS) 转移的患者被排除在外。 怀孕或哺乳期的女性被排除在外。 患有高血压（>150 mmHG 收缩压或>100 mmHG 舒张压）的患者以及在进入研究后 6 个月内有胃肠道穿孔、腹瘘或腹内脓肿病史的患者被排除在外。
只要患者在研究治疗开始时抗凝剂水平稳定至少 2 周，就允许在研究开始时进行全面抗凝治疗。
研究类型
介入性
注册 (实际的)
100
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Salzburg、奥地利、5020
- Paracelsus Medical University Salzburg-Oncology, Coop. Group
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Vienna、奥地利、1090
- Medical University Vienna, General Hospital
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Vienna、奥地利、1130
- State Hospital Vienna-Hietzing
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Vienna、奥地利、1090
- Med. Univ. Vienna; General Hospital Vienna
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Styria
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Graz、Styria、奥地利、8036
- Medical University of Graz-Oncology; Coop. Group
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Leoben、Styria、奥地利、8700
- State Hospital Leoben
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Tyrol
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Innsbruck、Tyrol、奥地利、6020
- Gynaegological Medical University Innsbruck
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Kufstein、Tyrol、奥地利、6330
- District Hospital Kufstein
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Upper Austria
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Linz、Upper Austria、奥地利、4010
- Hospital BHS Linz, Coop. Study Group
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Linz、Upper Austria、奥地利、4020
- AKH Linz
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Vorarlberg
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Feldkirch、Vorarlberg、奥地利、6807
- State Hospital Feldkirch, Coop. Group
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
纳入标准：
- 女性或男性，年龄≥18岁
- 经病理证实的浸润性原发性乳腺癌（炎性乳腺癌除外，T4d）计划接受含紫杉烷的新辅助全身治疗，有/无可触及淋巴结。
- 通过免疫组织化学 (IHC) 3+ 或通过当地实验室证实的原发肿瘤 HER2/c-erbB2 基因扩增确定的 HER2 蛋白过表达记录。
- 随机分组前 4 周内通过超声心动图或 MUGA 测量的 LVEF ≥ 55%
- ECOG 体能状态 ≤ 1
- 能够并愿意遵守预定的访问、治疗计划、实验室测试和其他研究程序。
- 书面知情同意书
排除标准：
目前治疗
- 同时使用抗病毒药物索利夫定或化学相关类似物（如溴夫定）的要求。
- 皮质类固醇的长期日常治疗，不包括。 吸入类固醇。
- 使用阿司匹林和阿司匹林类似物或氯吡格雷进行长期每日治疗
- 随机分组前 28 天内进行过重大外科手术、开放式活检或重大外伤，或预计在研究治疗过程中需要进行重大手术
- 当前或最近（随机化前 30 天内）使用另一种研究药物治疗或参与另一项研究。
实验室
- 骨髓功能不足
- 肝功能不足
- 肾功能不足
- 在第 1 周期的第 1 天之前的 7 天内激活了部分凝血活酶时间 (aPTT) 且未接受抗凝药物治疗的患者。
伴随条件
- 随机化前最后 5 年内的其他恶性肿瘤，但经治愈的宫颈原位癌或非黑素瘤性皮肤癌除外
- 临床判断远处转移的证据，至少通过胸部 X 光检查、肝脏超声检查和骨扫描。 如果临床上怀疑有脑转移，则必须在随机分组前 4 周内进行脑部 CT 扫描或 MRI。
可能影响方案依从性或结果解释的严重并发疾病，包括但不限于：
- 需要静脉注射的活动性感染 抗生素
- 不受控制的高血压
- 具有临床意义的心血管疾病史，如： 脑血管意外或中风；心肌梗塞;不稳定型心绞痛; NYHA II 级或更高 CHF；需要药物治疗的心律失常；有临床意义的瓣膜性心脏病。
- 静息时呼吸困难需要支持性氧疗或伴有明显胸腔积液
- 糖尿病控制不佳
- 与癌症无关的中枢神经系统疾病的身体/神经学检查的病史或证据（例如 不受控制的癫痫发作），除非经过标准药物治疗得到充分治疗
- 有出血风险的遗传性出血素质或凝血病史或证据
- 随机分组后 6 个月内有腹瘘、胃肠道穿孔或腹腔内脓肿史
- 严重的不愈合伤口、消化性溃疡或骨折
- 具有临床意义的吸收不良综合征、溃疡性结肠炎、影响胃肠功能的疾病、胃或小肠切除术或无法口服药物
- 未纠正的低钾血症或低镁血症
- 需要免疫抑制治疗的器官移植
- 任何其他疾病、代谢或心理功能障碍、体格检查结果或临床实验室结果合理怀疑禁忌使用研究药物的疾病或病症的证据，可能会影响患者对研究程序的依从性，或使患者处于高治疗相关并发症的风险。
- 已知对任何研究药物/赋形剂过敏。
- 对中国仓鼠卵巢细胞产品或其他重组人或人源化抗体过敏。
其他
- 妊娠试验未呈阴性的怀孕、哺乳期女性或有生育能力的女性
- 有生育能力的可育男性或女性
- 无法接受治疗或随访的患者
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
其他：A：曲妥珠单抗+多西紫杉醇
|
6 个周期 - 第 1 天（第 22 天 = 第 1 天）：曲妥珠单抗：8 mg/kg 负荷剂量（第一个周期）静脉注射；在随后的周期中静脉注射 6 mg/kg 维持剂量 多西紫杉醇：100 mg/m2，静脉注射 60 分钟 输液
其他名称：
|
|
实验性的：B：曲妥珠单抗+多西紫杉醇+贝伐珠单抗
|
6 个周期 - 第 1 天（第 22 天 = 第 1 天）：曲妥珠单抗：8 mg/kg 负荷剂量（第一个周期）静脉注射；在随后的周期中静脉注射 6 mg/kg 维持剂量 多西紫杉醇：100 mg/m2，静脉注射 60 分钟 输注贝伐珠单抗 15 mg/kg
其他名称：
|
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实验性的：C：曲妥珠单抗+多西紫杉醇+NPLD
|
6 个周期 - 第 1 天（第 22 天=第 1 天）：曲妥珠单抗：8 mg/kg 负荷剂量（第一个周期）静脉注射；在随后的周期中静脉注射 6 mg/kg 维持剂量 多西紫杉醇：75 mg/m2 60 分钟静脉输注 NPLD 50 mg/m2 60 分钟静脉输注 输液
其他名称：
|
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实验性的：D：曲妥珠单抗+多西紫杉醇+NPLD+贝伐珠单抗
|
6 个周期 - 第 1 天（第 22 天 = 第 1 天）：曲妥珠单抗：8 mg/kg 负荷剂量（第一个周期）静脉注射；在随后的周期中静脉注射 6 mg/kg 维持剂量 多西紫杉醇：75 mg/m2，静脉注射 60 分钟 输注 NPLD：50 mg/m2 60 分钟 i.v. 输液；贝伐珠单抗 15 毫克/千克
其他名称：
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
心脏毒性
大体时间：在第 1 周期的第 1 天和最后一次手术后的第 28 天之间
|
与标准疗法相比，曲妥珠单抗+多西他赛+贝伐珠单抗和曲妥珠单抗+多西紫杉醇+NPLD +/-贝伐珠单抗联合使用出现在第 1 周期第 1 天和第 28 天之间的复合终点评估心脏毒性最后的手术。
|
在第 1 周期的第 1 天和最后一次手术后的第 28 天之间
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
病理完全缓解 (ypCR)
大体时间：长达 22 周
|
ypCR 定义为在最后一次手术时没有浸润性肿瘤
|
长达 22 周
|
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总病理完全缓解 (ytpCR)
大体时间：长达 22 周
|
ytpCR 定义为乳腺和腋窝淋巴结中没有浸润性肿瘤和肿瘤细胞（ypT0 或 yDCIS 和 ypN=0）
|
长达 22 周
|
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总体临床缓解率 (cORR)
大体时间：长达 22 周
|
cORR 定义为具有完全临床反应 (cCR) 或部分临床反应 (cPR) 但没有 ypCR 的患者百分比
|
长达 22 周
|
|
根据AE、SAE、实验室检查异常、心脏评估、临床评估的患者数量进行安全性评估
大体时间：长达 22 周
|
最后一次手术时曲妥珠单抗和多西他赛联合贝伐单抗和曲妥珠单抗、多西他赛和 NPLD 加/减贝伐单抗的安全性（AE、SAE、实验室测试异常、心脏评估、临床评估）
|
长达 22 周
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Guenther Steger, MD、Austrian Breast & Colorectal Cancer Study Group
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
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