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A Study Evaluating the Effect of Pembrolizumab (MK-3475) in Participants With Renal Cell Cancer (MK-3475-031)

2020年6月22日 更新者:Merck Sharp & Dohme LLC

A Clinical Trial to Evaluate the Effect of Neoadjuvant MK-3475 (Pembrolizumab) Therapy on Intratumoral Immune Infiltrates in Renal Cell Cancer (RCC) Patients Undergoing Surgical Resection

This study will examine the effect of treatment with the neoadjuvant antibody pembrolizumab (MK-3475) on tumors of participants with renal cell cancer (RCC). The primary hypotheses are that pembrolizumab is well tolerated in participants undergoing RCC tumor resection; and that pembrolizumab will stimulate a 2-fold or greater increase in intratumoral lymphocytic infiltration in at least 30% of participants with RCC.

研究概览

研究类型

介入性

注册 (实际的)

10

阶段

  • 阶段1

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

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Have a newly diagnosed RCC, with a primary tumor diameter of more than 4 cm (>= T1b), not previously treated, and be a candidate for operative tumor resection
  • Be willing and able to undergo pre-treatment baseline image-guided core biopsy of their primary RCC
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
  • Demonstrate adequate organ function
  • Female is not breast feeding, is postmenopausal or surgically sterile; demonstrates non-pregnant state, and agrees to use two acceptable methods of birth control throughout the trial, until 120 days after the last dose of treatment
  • Male with female partner of childbearing potential agrees to use adequate method of contraception throughout study, until 120 days after last dose of treatment or last blood draw.

Exclusion Criteria:

  • Is currently participating in, or has participated in a study with an investigational agent or device within 4 weeks prior to first dose of study therapy
  • Has a diagnosis of immunosuppression or has received systemic steroid therapy, or any other form of immunosuppressive therapy within 4 weeks prior to first dose of study therapy
  • Has had prior chemotherapy, targeted small molecule, or radiation therapy for treatment of RCC
  • Has a known additional (other than RCC) malignancy that is progressing or requires active treatment
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has an active, or documented history of autoimmune disease, with the exceptions of vitiligo or resolved childhood asthma/atopy
  • Has a history of (non-infectious) pneumonitis that required treatment with steroids or current pneumonitis.
  • Has an active infection requiring systematic therapy
  • Is receiving anticoagulant therapy, with the exception of low dosage aspirin
  • Has severe cardiovascular disease or symptomatic ischemic heart disease
  • Has hepatic decompensation
  • Has uncontrolled thyroid dysfunction
  • Has uncontrolled diabetes mellitus
  • Has known psychiatric or substance abuse disorders
  • Female is pregnant or breastfeeding
  • Is expecting to conceive children within the projected maximum duration of the trial, extending through 120 days after the last dose of treatment or the last blood draw
  • Has received prior therapy with any antibody or drug (including ipilimumab) specifically targeting T-cell co-stimulation or checkpoint pathway
  • Has a known history of human immunodeficiency virus (HIV)
  • Has known active hepatitis B or C
  • Has received a live vaccine within 30 days prior to screening

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
实验性的:Neoadjuvant Pembrolizumab + RCC Resection
Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04.
200 mg administered by IV, once every 3-week cycle for a maximum of 2 cycles
其他名称:
  • MK-3475
  • 可瑞达®
Standard of care surgical resection of RCC tumor
200 mg administered by IV, once every 3-week cycle for a maximum of 17 cycles
其他名称:
  • MK-3475
  • 可瑞达®
实验性的:RCC Resection
Participants received SOC renal cell carcinoma (RCC) surgical resection; and then may have received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled under Protocol Amendment 04.
Standard of care surgical resection of RCC tumor
200 mg administered by IV, once every 3-week cycle for a maximum of 17 cycles
其他名称:
  • MK-3475
  • 可瑞达®

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
Number of Participants With an Adverse Event (AE) During the Neoadjuvant Pembrolizumab Regimen
大体时间:Up to Week 16
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE during their regimen of neoadjuvant pembrolizumab was presented.
Up to Week 16
Number of Participants Who Discontinued Treatment Due to an Adverse Event
大体时间:Up to 56 weeks
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study drug due to an adverse event is presented.
Up to 56 weeks
Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD3+ Lymphocytic Infiltration
大体时间:Baseline and Week 7
The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD3+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.
Baseline and Week 7
Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD8+ Lymphocytic Infiltration
大体时间:Baseline and Week 7
The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD8+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.
Baseline and Week 7
Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral FoxP3+ Lymphocytic Infiltration
大体时间:Baseline and Week 7
The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral FoxP3+ (forkhead box protein P3 positive) lymphocytic infiltration is presented. Evaluations were based on pathologist score.
Baseline and Week 7

次要结果测量

结果测量
措施说明
大体时间
Change From Baseline in Levels of Gene Expression of Immune Modulatory Receptors in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
大体时间:Baseline and Week 7
The change from baseline in levels of gene expression of immune modulatory receptors in tumors of participants treated with neoadjuvant pembrolizumab was presented.
Baseline and Week 7
Change From Baseline in Number of T Cells in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
大体时间:Baseline and Week 7
The change from baseline in number of T cells in tumors of participants treated with neoadjuvant pembrolizumab was presented.
Baseline and Week 7
Change From Baseline in Number of Activated T Cells in Peripheral Blood of Participants Treated With Neoadjuvant Pembrolizumab
大体时间:Baseline and Week 7
The change from baseline in the number of activated T cells in peripheral blood of participants treated with neoadjuvant pembrolizumab was presented.
Baseline and Week 7
Change From Baseline in Levels of Programmed Cell Death 1 Ligand 1 (PD-L1) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
大体时间:Baseline and Week 7
The change from baseline in levels of programmed cell death 1 ligand 1 (PD-L1) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.
Baseline and Week 7
Change From Baseline in Levels of Programmed Cell Death 1 Ligand 2 (PD-L2) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
大体时间:Baseline and Week 7
The change from baseline in levels of programmed cell death 1 ligand 2 (PD-L2) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.
Baseline and Week 7

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。

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)

2014年12月3日

初级完成 (实际的)

2019年7月5日

研究完成 (实际的)

2019年7月5日

研究注册日期

首次提交

2014年8月6日

首先提交符合 QC 标准的

2014年8月6日

首次发布 (估计)

2014年8月8日

研究记录更新

最后更新发布 (实际的)

2020年7月16日

上次提交的符合 QC 标准的更新

2020年6月22日

最后验证

2020年6月1日

更多信息

与本研究相关的术语

其他研究编号

  • 3475-031
  • 2014-002526-12 (EudraCT编号)
  • MK-3475-031 (其他标识符:Merck)
  • KEYNOTE-031 (其他标识符:Merck)

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

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

药物和器械信息、研究文件

研究美国 FDA 监管的设备产品

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.

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