Lurbinectedin 治疗具有 DNA 修复突变的晚期胰腺癌患者
Lurbinectedin (Zepzelca™ PM01183) 在具有 DNA 修复突变的晚期胰腺癌患者中的 II 期临床试验
研究概览
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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Arizona
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Scottsdale、Arizona、美国、85258
- HonorHealth Research Institute
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
描述
纳入标准：
- 在任何研究特定程序之前获得的患者自愿书面知情同意书 (ICF)。
- 年龄≥18岁；男女不限。
- 东部肿瘤协作组 (ECOG) 体能状态 (PS) 评分≤1
- 经组织学或细胞学证实的胰腺外分泌癌
- 进入研究时局部晚期不可切除或转移性疾病
- 在进入研究之前，ATM、ATR、CHEK2、BRCA1、BRCA2、RAD51、BRIP1、PALB2、PTEN、FANC、NBN、EMSY、MRE11 或 ARID1A 中已知有害或疑似有害（或等效解释）的 DNA 修复突变
- 最多三个针对晚期疾病的既往全身化疗线。
- 疾病进展到先前的治疗。 如果放射学评估确认疾病稳定或疾病进展（即对治疗无反应），则由于无法耐受的毒性而不再能够继续先前治疗的患者可考虑参与研究。
- 根据 RECIST 1.1 标准可测量的肿瘤病变。
足够的血液学、肾、代谢和肝功能，定义为：
- 血红蛋白≥9 g/dL（如果有临床指征，患者之前可能接受过红细胞 [RBC] 输注）；中性粒细胞绝对计数 (ANC) ≥1.5 x 109/L，血小板计数≥100 x 109/L。
- 丙氨酸氨基转移酶 (ALT) 和天冬氨酸氨基转移酶 (AST) ≤3.0 x 正常上限 (ULN)。
- 总胆红素≤ULN。
- 白蛋白≥3.0 g/dL。
- 计算的肌酐清除率 (CrCL) ≥30 mL/min（根据 Cockcroft 和 Gault 的公式）。
11. 第 1 周期第 1 天之前的清除期：
- 自上次化疗和/或研究药物以来至少三周。
- 自上次放疗 (RT) > 30 Gy 后至少 4 周。
- 自上次姑息性放疗后至少两周（≤ 10 次分割或 ≤ 30 Gy 总剂量）。
- 既往恶性肿瘤治疗成功且目前病情稳定且未接受积极治疗的患者符合条件。
- 根据美国国家癌症研究所不良事件通用术语标准 (NCI- CTCAE，第 5 版）。
有生育潜力的女性 (WOCBP) 的非生育状态证据。 WOCBP 必须同意在试验期间和治疗停止后最多六周内使用高效避孕措施*，并且有 WOCBP 伴侣的可育男性患者必须同意在试验期间和最多四个月后不生孩子或捐献精子治疗中止。
- 高效方法：与抑制排卵相关的联合（含雌激素和孕激素）激素避孕；与抑制排卵相关的仅含孕激素的激素避孕药；宫内节育器 (IUD)；宫内激素释放系统 (IUS)；双侧输卵管阻塞；输精管结扎的伴侣；禁欲
排除标准：
- 既往接受过 lurbinectedin 或 trabectedin 治疗
- 先前使用聚（ADP-核糖）聚合酶 (PARP) 抑制剂治疗
- 组织学中的神经内分泌分化或粘液亚型
- 超过三个先前的晚期疾病全身化疗线
- 已知的脑转移或软脑膜疾病受累
伴随疾病/病症：
- 心脏病史：入组前一年内有心肌梗塞或症状性/不受控制的心绞痛；左心室射血分数 (LVEF) ≤ 50% 的疼痛史，通过多门采集扫描 (MUGA) 或等效超声（US）评估；或症状性心律失常。
- 全身性水肿和/或临床明显的腹水或在进入研究前三周内需要引流。 由腹水引起的永久性外部引流也被排除在外。
- 免疫功能低下的患者，包括已知感染人类免疫缺陷病毒 (HIV) 的患者。
- 已知慢性活动性乙型肝炎病毒（HBV）或丙型肝炎病毒（HCV）。 对于乙型肝炎，这包括乙型肝炎表面抗原和定量乙型肝炎聚合酶链反应 (PCR) 的阳性检测。 对于丙型肝炎，这包括丙型肝炎抗体和定量丙型肝炎 PCR 的阳性检测。
- 活动性不受控制的感染。
- 患者依从治疗或遵循方案的能力受到限制。
- 根据研究者的判断，任何其他重大疾病将大大增加与患者参与本研究相关的风险。
- 患有急性病和/或立即处于生命窘迫状态的患者，包括临床状况迅速恶化或在治疗登记前两周内因疾病症状无法控制而可能需要计划外住院的患者。
- 孕妇或哺乳期妇女。
- 进入研究后 3 周内接种活疫苗
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：Lurbinectedin
Lurbinectedin 将在每个周期的第 1 天（一个周期 = 3 周±48 小时）以 1 小时（±10 分钟）输注的形式静脉内 (IV) 给药。
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Lurbinectedin 将以最小总体积为 100 mL 的输注溶液（5% 葡萄糖或 0.9% 氯化钠）给药。 Lurbinectedin 将以固定输注速率以 3.2 mg/m2 的剂量通过外周或中心静脉内给药。
其他名称：
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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 |
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Overall Response Rate (ORR) at 12 Weeks
大体时间：12 weeks
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The antitumor activity of lurbinectedin was measured in terms of overall response rate (ORR) at 12 weeks. ORR was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) according to RECIST v.1.1. CR was defined as the complete radiologic disappearance of all target lesions, while PR was defined as at least a 30% decrease in the sum of the longest diameter of target lesions. |
12 weeks
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Duration of Response (DOR)
大体时间：From initiation of study treatment up to study completion, up to 20 months
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Duration of response (DOR) was defined as the time from when a participant was reported to respond to lurbinectedin treatment (complete response (CR) or partial response (PR) by RECIST v1.1) to the time when they experienced progressive disease (PD) or death. CR was defined as the complete radiologic disappearance of all target lesions, PR as at least a 30% decrease in the sum of the longest diameter of target lesions, and PD as at least a 20% increase in the sum of the longest diameter of target lesions. |
From initiation of study treatment up to study completion, up to 20 months
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Clinical Benefit
大体时间：From 4 months up to 20 months
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Clinical benefit was defined as the percentage of patients with a complete response (CR), partial response (PR), or stable disease (SD), as measured by RECIST v.1.1, for ≥4 months. CR was defined as the complete radiologic disappearance of all target lesions, PR as at least a 30% decrease in the sum of the longest diameter of target lesions, and SD as no change in the sum of the longest diameter of target lesions. |
From 4 months up to 20 months
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Normalization of Tumor Markers
大体时间：From initiation of study treatment until end of study treatment, up to 9.1 weeks
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The number of participants with > 2 x ULN tumor marker values at baseline who had their tumor marker values normalize to at or below ULN after receiving lurbinectedin therapy. Tumor markers included CA19-9 and CEA for non-expressors of CA 19-9. ULN was defined at 35 U/mL for CA 19-9 and 3 ng/mL for CEA. |
From initiation of study treatment until end of study treatment, up to 9.1 weeks
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Progression-free Survival (PFS)
大体时间：From initiation of study treatment to disease progression/death/last tumor evaluation, up to 4.1 months
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Progression-free survival (PFS) was defined as the time from the first infusion of lurbinectedin to the date of progressive disease, death (of any cause), or last tumor evaluation.
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From initiation of study treatment to disease progression/death/last tumor evaluation, up to 4.1 months
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Progression-free Survival Rate at Three Months (PFS3)
大体时间：3 months
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Progression-free survival rate at three months (PFS3) was defined as the percentage of patients who were alive and progression-free three months after the first infusion of lurbinectedin.
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3 months
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Overall Survival (OS)
大体时间：From initiation of study treatment to date of death/last patient contact, up to 20 months
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Overall survival (OS) was defined as the time from the first infusion of lurbinectedin to the date of death (of any cause) or last patient contact.
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From initiation of study treatment to date of death/last patient contact, up to 20 months
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Overall Survival Rate at Six Months (OS6)
大体时间：6 months
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Overall survival rate at six months (OS6) was defined as the percentage of patients who were alive six months after the first infusion of lurbinectedin.
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6 months
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Overall Survival Rate at 12 Months (OS12)
大体时间：12 months
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Overall survival rate at 12 months (OS12) was defined as the percentage of patients who were alive 12 months after the first infusion of lurbinectedin.
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12 months
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Adverse Events Possibly or Definitely Related to Lurbinectedin
大体时间：From initiation of study treatment to end of follow-up, up to 20 months
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Adverse events (AEs) were graded and collected according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0). AEs that were determined to be possibly or definitely related to lurbinectedin are reported here. The AE grading scale for NCI-CTCAE v5.0 is as follows: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe, non-life threatening; Grade 4 - life-threatening; Grade 5 - death. |
From initiation of study treatment to end of follow-up, up to 20 months
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合作者和调查者
调查人员
- 首席研究员：Erkut Borazanci, MD、HonorHealth Research Institute
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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