此页面是自动翻译的，不保证翻译的准确性。请参阅 英文版 对于源文本。

A Study of [14 C]-Pevonedistat in Participants With Advanced Solid Tumors

2019年11月4日 更新者：Millennium Pharmaceuticals, Inc.

A Phase 1 Study to Assess Mass Balance, Pharmacokinetics, and Metabolism of [14C]-Pevonedistat in Patients With Advanced Solid Tumors

The purpose of this study is to assess the mass balance (that is, cumulative excretion of total radioactivity [TRA] in urine and feces) and to characterize the pharmacokinetics (PK) of pevonedistat in whole blood, plasma, and urine, and of TRA in plasma and whole blood following a single 1-hour infusion of 25 milligram per square meter (mg/m^2) [14C]-pevonedistat intravenous (IV) solution containing approximately 60 to 85 microcurie (mCi) (approximately 2.22-3.145 megabecquerel [MBq]) of TRA in participants with advanced solid tumors in Part A.

研究概览

地位

完全的

条件

干预/治疗

详细说明

The drug being tested in this study is called Pevonedistat. Pevonedistat is being tested to treat people with advanced solid tumors.

The study will enroll approximately 4 to 6 pharmacokinetics (PK)-evaluable participants in part A. After completion of the mass balance and absorption, distribution, metabolism, excretion (ADME) assessment in Part A of the study, eligible participants will have the opportunity to continue into Part B at a secondary study site, which would begin in approximately 2 weeks of completion of Part A.

  • [14C]-Pevonedistat 25 mg/m^2
  • Part B (optional): Pevonedistat in combination with chemotherapy regimens (Pevonedistat 25 mg/m^2 + docetaxel 75 mg/m^2 or pevonedistat 20 mg/m^2 + carboplatin 20 mg/m^2 + paclitaxel 175 mg/m^2)

All participants will receive study drug via intravenous route. This multi-center trial will be conducted in Hungary. Participants will remain confined to the study site for 9 to 14 days in Part A. Participation in Part B is optional, participants will be re-evaluated for inclusion/exclusion criteria before administrating treatment. Participants will undergo treatment in Part B for a maximum of 12 cycles (21 days cycle each) and will include approximately 36 weeks for Part A and B combined. Participants will attend an end of study visit 30 days after the last dose of study drug in both Part A and B.

研究类型

介入性

注册 (实际的)

8

阶段

  • 阶段1

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

  • 匈牙利
      • Budapest、匈牙利、1062
        • Magyar Honvedseg Egeszsegugyi Kozpont Onkologiai Osztaly
      • Budapest、匈牙利、1076
        • PRA Magyarország Kft. Fázis I-es Klinikai Farmakológiai Vizsgálóhely

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

Inclusion Criteria:

  1. Have a histologically or cytologically confirmed metastatic or locally advanced and incurable solid tumor that is felt to be appropriate for treatment with one of the 2 chemotherapy regimens in Part B of this study (carboplatin+paclitaxel or docetaxel), or have progressed despite prior standard therapy, or for whom conventional therapy is not considered effective. The tumor must be radiographically or clinically evaluable and/or measurable.
  2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  3. Expected survival longer than 3 months from enrollment in the study.
  4. Recovered (that is, less than or equal to [<=] Grade 1 toxicity) from the effects of prior antineoplastic therapy.

Exclusion Criteria:

  1. Has irregular defecation patterns (less than 1 defecation per 2 days or excessive diarrhea) and/or has a history of changes in bowel habits with daily routine or environment changes.
  2. Prior treatment with radiation therapy involving greater than or equal to (>=) 25% of the hematopoietically active bone marrow.

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：其他
  • 介入模型：顺序分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：[14C]-Pevonedistat 25 mg/m^2
[14C]-pevonedistat (containing approximately 60-98 mCi [approximately 2.22-3.626 MBq] of radioactive tracer), infusion, intravenously, single dose on Day 1 of Week 1 in Part A. After completion of Part A, participants will have opportunity to continue into Part B. Participant will receive Pevonedistat 25 mg/m^2, infusion, intravenously, single dose on Days 1, 3 and 5 of each 21 day cycle, for up to 12 cycles along with docetaxel 75 mg/m^2, infusion, intravenously, over 1 hour on Day 1 of each 21 day cycle; or pevonedistat 20 mg/m^2, infusion, intravenously, single dose on Days 1, 3 and 5 of each 21 day cycle, for up to 12 cycles, followed by paclitaxel 175 mg/m^2, infusion, intravenously, over 3 hours along with carboplatin 20 mg/m^2, infusion, intravenously, over 30 minutes on Day 1 of 21 each cycle up to 12 cycles. Based on investigator and sponsor discretion, participants deriving benefits will continue to receive current combination therapy or pevonedistat alone beyond 12 cycles.
药品：培酮司他
Pevonedistat 静脉输注。
其他名称：
  • MLN4924； TAK-924
药品：多西紫杉醇
多西紫杉醇静脉滴注。
药品：卡铂
卡铂静脉滴注。
药品：紫杉醇
紫杉醇静脉滴注。
药品：[14C]-Pevonedistat
[14C]-Pevonedistat intravenous infusion.

研究衡量的是什么？

主要结果指标

结果测量
大体时间
Part A: Cmax: Maximum Observed Plasma and Whole Blood Concentration for Pevonedistat
大体时间：Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part A: Tmax: Time to Reach the Maximum Plasma and Whole Blood Concentration (Cmax) for Pevonedistat
大体时间：Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part A: AUClast: Area Under the Plasma and Whole Blood Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Pevonedistat
大体时间：Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part A: Cmax: Maximum Observed Plasma and Whole Blood TRA Concentration for [14C]-Pevonedistat Drug-related Material
大体时间：Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part A: Tmax: Time to Reach the Maximum Plasma and Whole Blood TRA Concentration (Cmax) for [14C]-Pevonedistat Drug-related Material
大体时间：Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part A: AUClast: Area Under the Plasma and Whole Blood TRA Concentration Curve From Time 0 to Time of the Last Quantifiable Concentration for [14C]-Pevonedistat Drug-related Material
大体时间：Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part A: Aeurine,14C: Cumulative Amount of [14C]-Pevonedistat Excreted in Urine up to the Last Sampling Interval
大体时间：Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part A: Aefeces,14C: Cumulative Amount of [14C]-Pevonedistat Excreted in Feces up to the Last Sampling Interval
大体时间：Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part A: Aetotal,14C: Total Cumulative Excretion of [14C]-Pevonedistat From the Body
大体时间：Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part A: Aeurine: Cumulative Amount of Pevonedistat Dose Excreted in Urine at 144-168 Hours Post-dose
大体时间：Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part A: Feurine: Cumulative Percentage of Pevonedistat Dose Excreted in Urine at 144-168 Hours Post-dose
大体时间：Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part A: Renal Clearance (CLR) for Pevonedistat
大体时间：Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

次要结果测量

结果测量
措施说明
大体时间
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
大体时间：Part A: From first dose of study drug in Part A up to Day 31; Part B: From first dose of study drug in Part B up to Cycle 11 Day 35 (Cycle length is equal to [=] 21 days)
Part A: From first dose of study drug in Part A up to Day 31; Part B: From first dose of study drug in Part B up to Cycle 11 Day 35 (Cycle length is equal to [=] 21 days)
Part A: Percent Distribution of Total Radioactivity (TRA) for Pevonedistat and Its Metabolites in Plasma, Urine and Feces
大体时间：Up to 168 hours post-dose
Up to 168 hours post-dose
Part B: Number of Participants With Best Overall Response as Per Investigator's Assessment
大体时间：Up to Cycle 11 (Cycle length =21 days)
The best overall response was defined as the participants with best response among complete response (CR) or partial response (PR) or stable disease (SD), or progressive disease (PD). It was assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than (<) 10 millimeter (mm). PR: at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters as the best overall response after randomization. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
Up to Cycle 11 (Cycle length =21 days)

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。

赞助

Millennium Pharmaceuticals, Inc.

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

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2017年5月11日

初级完成 (实际的)

2018年2月8日

研究完成 (实际的)

2018年11月5日

研究注册日期

首次提交

2017年2月14日

首先提交符合 QC 标准的

2017年2月15日

首次发布 (实际的)

2017年2月20日

研究记录更新

最后更新发布 (实际的)

2019年11月18日

上次提交的符合 QC 标准的更新

2019年11月4日

最后验证

2019年11月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • Pevonedistat-1013
  • U1111-1169-6648 (注册表标识符：WHO)
  • 2016-004132-37 (EudraCT编号)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

是的

IPD 计划说明

Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

培酮司他的临床试验

搜索类似试验

赞助者和合作者

医疗条件

药物干预

CROs by country

CROs in Poland

条件

罕见疾病

药物干预

膳食补充剂

赞助者/合作者

地点

订阅