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Stereotactic Radiosurgery With Nivolumab and Valproate in Patients With Recurrent Glioblastoma

2017年5月26日 更新者：Benjamin Purow, MD、University of Virginia

A Pilot Study to Evaluate the Feasibility of the Combined Use of Stereotactic Radiosurgery With Nivolumab and Concurrent Valproate in Patients With Recurrent Glioblastoma

The purpose of this study is to evaluate the safety and feasibility of the immunotherapeutic agent nivolumab given in combination with gamma knife therapy and valproate in patients with recurrent glioblastoma, a common and lethal type of brain cancer.

研究概览

地位

终止

条件

干预/治疗

详细说明

Immune checkpoint inhibitors have the potential to treat a wide range of diverse cancers. Of particular interest to researchers is the PD-1 receptor-ligand interaction, a major pathway that many cancers hijack in order to suppress immune control. Anti-PD-1 antibodies such as nivolumab show a strong potential to treat many types of cancers including glioblastoma, the most common and most lethal brain cancer.

This study will examine a means of further focusing immune response on glioblastoma by combining stereotactic "gamma knife" radiosurgery with nivolumab. The rationale behind this intervention is that the radiation therapy will enhance immune response rate by providing additional tumor antigens from dying cells. Additionally, a study from investigators at Johns Hopkins indicates that histone deacetylase (HDAC) inhibitors may boost the anti-cancer efficacy of PD-1 antibodies like nivolumab. Valproate, a class I HDAC inhibitor, will be used concurrently with nivolumab with the goal of enhancing the effects of both the nivolumab and the radiotherapy.

研究类型

介入性

注册 (实际的)

4

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

  • 美国
    • Virginia
      • Charlottesville、Virginia、美国、22908
        • University of Virginia

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:

  • Confirmed malignant, recurrent glioblastoma or gliosarcoma
  • Subject must have adequate organ function
  • Subject must still be able to care for most of his or her personal needs

Exclusion Criteria:

  • Subject is pregnant
  • Subject has extracranial metastatic or leptomeningeal disease
  • Subject has an additional malignancy that is progressing or requires active treatment, exceptions being basal cell and squamous cell carcinomas of the skin, indolent prostate cancer, chronic lymphocytic leukemia, or in situ cervical cancer
  • Subject has received chemotherapy, biological therapy, or had surgery 4 weeks prior to beginning the study
  • Subject has had radiation therapy within 10 weeks prior to entering beginning the study
  • Subject has had prior therapy with bevacizumab
  • Subject has had previous treatment with carmustine wafer except when administered as first-line treatment no less than six months prior to beginning the study
  • Subject requires escalating supraphysiologic doses of corticosteroids greater than 2 mg of dexamethasone or an equivalent
  • Active autoimmune disease requiring systemic treatment within the past 3 months or any syndrome that requires immunosuppressive agents
  • Interstitial lung disease or active, non-infectious pneumonitis
  • Evidence of greater than Grade 1 CNS hemorrhage or greater than Grade 3 venous thromboembolism
  • History of uncontrolled cardiac disease
  • Subject unable or unwilling to have a head contrast enhanced MRI

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：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
实验性的：Nivolumab & Valproate Following G.K.
Subjects will begin a valproate regimen prior to undergoing stereotactic radiosurgery (gamma knife) on a single lesion. Following the surgery, subjects will receive nivolumab every 2 weeks and daily valproate.
辐射：Stereotactic Radiosurgery
Subjects will receive a single large dose of radiation to one or more lesions.
其他名称：
  • Gamma Knife Radiosurgery
药品：Nivolumab
3 mg/kg of nivolumab will be administered through IV infusion every two weeks following stereotactic radiosurgery.
其他名称：
  • 欧狄沃
药品：Valproate
Subjects will begin regimen of valproate prior to radiosurgery and continue to receive therapy concurrently with nivolumab. Subjects will receive valproate daily with a target serum level of 75-100 μg/ml.
其他名称：
  • 丙戊酸钠
  • 丙戊酸
  • Divalproex Sodium

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
Feasibility based on number of subjects who complete 4 doses of nivolumab
大体时间：At 3 months following radiosurgery
Feasibility of the radiosurgery and drug combination will be determined based on the number of subjects who complete at least 4 doses of nivolumab.
At 3 months following radiosurgery
Incidence of adverse events
大体时间：From the beginning of treatment until no sooner than 30 days following the last study treatment
Safety will be assessed by imaging of necrosis, incidence and severity of adverse events, changes in laboratory findings, physical examinations, vital signs, and the number of discontinuations due to adverse events.
From the beginning of treatment until no sooner than 30 days following the last study treatment

次要结果测量

结果测量
措施说明
大体时间
Clinical Response Rate
大体时间：From the beginning of treatment until documented disease progression or date of death, assessed up to 48 months.
Response to therapy will be evaluated by means of RANO criteria.
From the beginning of treatment until documented disease progression or date of death, assessed up to 48 months.

其他结果措施

结果测量
措施说明
大体时间
Incidence of Pseudoprogressions
大体时间：From the beginning of treatment until documented disease progression or date of death, assessed up to 48 months.
Pseudoprogression, the transient increase in apparent tumor size, will be documented.
From the beginning of treatment until documented disease progression or date of death, assessed up to 48 months.

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

University of Virginia

调查人员

  • 首席研究员：Benjamin Purow, MD、University of Virginia

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)

2016年5月24日

初级完成 (实际的)

2017年2月21日

研究完成 (实际的)

2017年2月21日

研究注册日期

首次提交

2015年12月16日

首先提交符合 QC 标准的

2016年1月6日

首次发布 (估计)

2016年1月7日

研究记录更新

最后更新发布 (实际的)

2017年5月31日

上次提交的符合 QC 标准的更新

2017年5月26日

最后验证

2017年5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

  • 18574
  • CA209-378 (其他标识符：University of Virginia)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

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.

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