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临床试验/NCT01120288
NCT01120288已完成1 期

A Pilot Study of EZN-2968, an Antisense Oligonucleotide Inhibitor of HIF-1alpha, in Adults With Advance Solid Tumors

National Cancer Institute (NCI)2 个研究点 分布在 1 个国家目标入组 10 人开始时间: 2010年4月29日最近更新:
适应症
相关药物

试验速览

阶段
1 期
状态
已完成
入组人数
10
试验地点
2
主要终点
Determine the modulation of HIF-1 alpha mRNA in tumor biopsies pre- and post- administration of EZN-2968.

研究概览

简要总结

Background:

  • A protein called HIF is believed to be involved both in forming cancers and helping them to grow after they are formed. EZN-2968 is a new type of cancer drug that goes into the cancer cell and switches off the production of the HIF protein. Researchers are interested in testing EZN-2968 in people who have liver cancer because studies have shown that this drug travels to the liver and stays there when the drug is given through a vein.

Objectives:

  • To determine the safety and effectiveness of EZN-2968 on liver cancer.

Eligibility:

  • Individuals 18 years of age and older who have been diagnosed with liver cancer that has not responded to standard treatments.

Design:

  • Participants will have an initial screening visit with a physical examination, blood and urine tests, and imaging studies to assess tumor size. Tumor biopsies may also be taken for research purposes.
  • Participants will have an undefined number of 6-week treatment cycles of EZN-2968, given once a week for 3 weeks followed by 3 weeks without the drug.
  • During each cycle, participants will have additional blood tests and imaging scans to assess tumor response to treatment.
  • Cycles of treatment with EZN-2968 may continue until the treatment is not effective, illness requires participants to stop taking the study drug, or the participant chooses to withdraw from the study.

详细描述

Background:

  • Hypoxia-inducible factor-1 (HIF-1) facilitates the adaptation of normal and tumor tissue to oxygen deprivation. HIF-1 is frequently overexpressed in cancer cells, where it is involved in the upregulation of many gene products essential for invasion, migration, angiogenesis, and survival, including vascular endothelial growth factor (VEGF). Blocking HIF-1 activity inhibits the expression of VEGF, resulting in the inhibition of tumor growth in vitro and in vivo.
  • EZN-2968 is an antisense oligonucleotide that specifically targets HIF-1 alpha, one of the subunits of HIF-1. Safety and preliminary suggestion of activity have been demonstrated in two Phase I trials; one patient with hepatocellular carcinoma, one with renal cell cancer, and one with angiosarcoma of the face treated with EZN-2968 had objective evidence of shrinkage of large masses. In vivo data show evidence of intracellular uptake of EZN-2968 into tumor cells, and in the Phase I trial, preliminary data show that eleven patients had prolonged stable disease (>90 days duration on study), three of which had objective evidence of tumor shrinkage, thus demonstrating proof of principle for this approach.

Primary Objective:

  • Determine the modulation of HIF-1alpha mRNA in tumor biopsies pre- and post-administration of EZN-2968.

Secondary Objectives:

研究设计

研究类型
Interventional
分配方式
Non Randomized
干预模型
Single Group
主要目的
Treatment
盲法
None

入排标准

年龄范围
18 Years 至 120 Years(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • 未提供

排除标准

  • 未提供

结局指标

主要结局

Determine the modulation of HIF-1 alpha mRNA in tumor biopsies pre- and post- administration of EZN-2968.

时间窗: 1-2 years

次要结局

  • Assess the safety of EZN-2968 in patients with liver-predominant solid tumors. Determine the modulation of HIF-1 alpha protein levels in tumor biopsies pre- and post-administration of EZN-2968.(1-2 years)

研究者

申办方类型
Nih
责任方
Sponsor

研究点 (2)

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