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Dose-Finding of Retinoid 9cUAB30 in Healthy Volunteers

2014年10月7日 更新者:National Cancer Institute (NCI)

A Randomized, Double-Blind, Single-dose and Multi-dose Study of the Novel Retinoid, 9cUAB30, to Determine Pharmacokinetics and Safety

This randomized phase I trial studies the side effects and the best dose of retinoid 9cUAB30 in healthy volunteers. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of retinoid 9cUAB30 may keep cancer from forming.

研究概览

详细说明

PRIMARY OBJECTIVES:

I. The primary objective is to determine the toxicities and recommended phase II dose of 9cUAB30. The co- primary objective is to characterize the urine and plasma single dose and steady state pharmacokinetics of 9cUAB30 in normal volunteers.

SECONDARY OBJECTIVES:

I. To correlate the pharmacokinetics of 9cUAB30 with toxicity. II. To compare observed toxicity between placebo controls and each dose level. III. To assess for any change in single dose PK after repeat dosing (Day 1 vs. Day 36).

IV. To assess the following potential biomarkers of UAB30:

  • Telomerase activity (measurement of telomeric repeats) in PBMCs.
  • Gene expression of DNA methyltransferase in PBMCs.
  • Gene expression of CYP2B6 in PBMCs.

OUTLINE: This is a dose-escalation study. Participants are randomized to 1 of 2 treatment arms.

ARM I: Participants receive retinoid 9cUAB30* orally (PO) on days 1-28.

ARM II: Participants receive placebo* PO on days 1-28.

Courses repeat every 28 days in the absence of unacceptable toxicity.

*NOTE: Participants receive doses on days 8, 15, 22 and 29 after they have fasted for 12 hours.

After completion of study treatment, patients are followed up on days 7 and 30.

研究类型

介入性

注册 (实际的)

50

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

    • Wisconsin
      • Madison、Wisconsin、美国、53792
        • University of Wisconsin Hospital and Clinics

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 至 65年 (成人、年长者)

接受健康志愿者

是的

有资格学习的性别

全部

描述

Inclusion Criteria:

  • ECOG performance status =< 1 (Karnofsky >= 70%)
  • WBC >= 3000/mm^3
  • Platelets >= 100,000mm^3
  • Bilirubin =< upper limit of institutional normal
  • AST =< upper limit of institutional normal
  • Creatinine within institutional normal limits
  • Sodium =< upper limit of institutional normal
  • Potassium =< upper limit of institutional normal
  • Chloride =< upper limit of institutional normal
  • Bicarbonate =< upper limit of institutional normal
  • Fasting triglycerides =<1.5 x ULN
  • Fasting cholesterol =< 1.5 x ULN
  • Participants must agree to discontinue all vitamin supplements while taking study medication and for thirty days past the last dose of study medication
  • The effects of 9cUAB30 on the developing human fetus are unknown; for this reason, women must agree to use TWO effective forms of birth control for the duration of study participation and for 30 days following the last dose of study medication

    • The following persons are not considered to be able to father or bear children and therefore are eligible to participate without the use of concurrent birth control:

      • Female with bilateral oophorectomy and/or hysterectomy
      • Female with fallopian tubes cut, tied, or sealed
      • Female with sterilization implant (e.g. Adiana, Essure) placed > 3 months prior to randomization
      • Female post-menopausal (> 1 year since last menses)
      • Male with vasectomy > 3 months prior to randomization
    • One of the following methods of birth control must be used by women of childbearing potential:

      • Combined oral contraceptive pill in continuous use for > 30 days prior to study entry
      • Vaginal ring (e.g. NuvaRing) in continuous use for > 30 days prior to study entry
      • Skin patch (e.g. Ortho Evra) in continuous use for > 30 days prior to study entry
      • Injection (e.g. Depo-Provera, Noristerat®) in continuous use for > 30 days prior to study entry
      • Copper IUD (e.g. ParaGard)
    • Note: because of the decreased effectiveness of low dose progesterone-only contraceptive methods when used with retinoids, the following hormonal methods are NOT acceptable:

      • Low dose progesterone only oral contraceptive pill ("mini pills" e.g. Micronor®, Nor-Q.D., Ovrette)
      • Norplant subdermal implant
      • Mirena® Hormonal Implanted Uterine Device (IUD)
    • In addition to the above method of contraception, one of the following methods of contraception will ALSO be used for the duration of study participation and for 30 days following the last dose of study medication:

      • Diaphragm, cervical cap, or cervical shield with spermicide
      • Contraceptive sponge (e.g. Today Sponge)
      • Condom (male or female type) plus spermicide
  • Females of child-bearing potential must have a negative pregnancy test within the current menstrual cycle and within 7 days before starting drug
  • Participants must have the ability to understand, and the willingness to sign, a written informed consent document

Exclusion Criteria:

  • Participants may not be taking medications that might interact with 9cUAB30; detailed list of potentially interacting medications
  • Participants may not be taking lipid lowering agents
  • Participants may not be receiving any other investigational agents
  • Participants with a history of allergic reactions attributed to compounds of similar chemical or biologic composition of retinoids
  • Participants with an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 9cUAB30, breastfeeding must be discontinued for the duration of study participation and for one month after the last dose of the study agent if the mother is treated with 9cUAB30
  • Individuals known to be HIV-positive may not participate in this study; the uncertain immune status of HIV-positive people and the potential risks of taking part in this study are too great to justify this non-treatment therapy
  • Individuals with a history of cancer diagnosis or reoccurrence < 5 years from study entry may not participate; however, individuals with a history of squamous or basal cell carcinoma of the skin < 5 years from study entry will not be excluded from this study; the effects of this study agent on the immune system of people at risk for recurring cancer are unknown

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:三倍

武器和干预

参与者组/臂
干预/治疗
实验性的:Arm I (retinoid 9cUAB30)
Participants receive retinoid 9cUAB30* PO on days 1-28.
相关研究
相关研究
其他名称:
  • 药理学研究
Given PO
Disease prevention
其他名称:
  • cancer prevention intervention
安慰剂比较:Arm II (placebo)
Participants receive placebo* PO on days 1-28.
相关研究
相关研究
其他名称:
  • 药理学研究
给定采购订单
其他名称:
  • PLCB
Disease prevention
其他名称:
  • cancer prevention intervention

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
Recommended phase II dose of 9cUAB30 based on the MTD
大体时间:28 days
28 days
Pharmacokinetics of 9cUAB30 in normal volunteers
大体时间:Baseline, days 1, 8, 15, 22, 36, and 43
Using one-sample t-tests, or Wilcoxon signed-rank tests as appropriate in order to evaluate the single vs. steady state levels. An appropriate regression model will be used to explore the relationship of dose with change in PK.
Baseline, days 1, 8, 15, 22, 36, and 43

次要结果测量

结果测量
措施说明
大体时间
Correlation between pharmacokinetic and toxicity as assessed by CTCAE
大体时间:Up to 36 days
Up to 36 days
Comparison of toxicity between placebo and controls as assessed by CTCAE
大体时间:Up to 36 days
To compare toxicities at each dose level to placebo, the Chi-square test will be used for the presence or absence of toxicities, and Wilcoxon rank-sum tests will be used for CTCAE grade and investigator defined relationship data.
Up to 36 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。

调查人员

  • 首席研究员:Jill Kolesar、University of Wisconsin, Madison

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

2011年10月1日

初级完成 (实际的)

2012年9月1日

研究完成 (实际的)

2012年9月1日

研究注册日期

首次提交

2011年3月24日

首先提交符合 QC 标准的

2011年4月13日

首次发布 (估计)

2011年4月15日

研究记录更新

最后更新发布 (估计)

2014年10月9日

上次提交的符合 QC 标准的更新

2014年10月7日

最后验证

2013年5月1日

更多信息

与本研究相关的术语

其他研究编号

  • NCI-2013-00468
  • N01CN35153 (美国 NIH 拨款/合同)
  • CO10311

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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