PHASE IB 9CUAB30 IN EARLY STAGE BREAST CANCER TO EVALUATE BIOLOGIC EFFECT

IB 期 9CUAB30 在早期乳腺癌中评估生物学效应

基本信息

批准号：
10249044
负责人：
HOWARD BAILEY
金额：
$ 27.19万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-12 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10249044
关键词：
Aftercare Agonist Animal Model Apoptosis Apoptotic Bexarotene Biological Biological Markers Breast Cancer Patient Breast Cancer Prevention Control Groups Custom Data Dose Enrollment Estrogen Receptor Status Estrogen receptor negative Estrogen receptor positive Gene Chips Gene Expression Genes Liver Mammary Gland Parenchyma Mammary Neoplasms Measures Molecular Analysis Molecular Conformation Oral Participant Patients Pharmaceutical Preparations Phase Proteins Protocols documentation RXR Retinoic Acid Receptor Retinoids Sampling TdT-Mediated dUTP Nick End Labeling Assay Technology Tissue Sample Tissues Work analog arm case control comparative design follow-up gene panel indexing malignant breast neoplasm nano-string novel prevent tissue biomarkers treatment duration tumor

Aftercare Agonist Animal Model Apoptosis Apoptotic Bexarotene Biological Biological Markers Breast Cancer Patient Breast Cancer Prevention Control Groups Custom Data Dose Enrollment Estrogen Receptor Status Estrogen receptor negative Estrogen receptor positive Gene Chips Gene Expression Genes Liver Mammary Gland Parenchyma Mammary Neoplasms Measures Molecular Analysis Molecular Conformation Oral Participant Patients Pharmaceutical Preparations Phase Proteins Protocols documentation RXR Retinoic Acid Receptor Retinoids Sampling TdT-Mediated dUTP Nick End Labeling Assay Technology Tissue Sample Tissues Work analog arm case control comparative design follow-up gene panel indexing malignant breast neoplasm nano-string novel prevent tissue biomarkers treatment duration tumor

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项目摘要

Retinoids, which target the retinoic acid receptors (RARs), and rexinoids, which target the retinoid X receptors (RXRs), represent two classes of potential drugs with potent capacity to prevent breast cancers and have been studied extensively. 9cUAB30 is a novel RXR-selective retinoid, which is a conformationally constrained analog of 9 cis UAB30. In animal models 9cUAB30 has been shown to prevent both ER-positive and ER-negative mammary cancers with similar potency to Targretin. Additionally, modulation of proliferation and apoptosis was seen after only 7 days of treatment. Importantly gene expression array profiling has been used to demonstrate that 9cUAB30 is not an agonist in liver, which is the desired hallmark of a tissue-selective rexinoid. This single arm phase IB study is designed to determine if 9cUAB30 at the selected dose modifies breast tissue biomarkers. Therefore, this statement of work outlines the requirements for the study, including (but not limited to) participant accrual, agent administration and patient follow-up as well as associated biomarker analyses. This statement of work includes protocol activities to screen 80 participants and enroll 40 on trial stratified by ER status of the tumor as well as perform biomarkers on matched control cases.

靶向视黄酸受体（RARS）的类维生素类视网膜类动物，靶向性类维生素X受体（RXR），代表了两种具有预防乳腺癌的潜在药物，并且已经进行了广泛的研究。 9CUAB30是一种新型的RXR选择性类维生素类似，它是9顺式UAB30的构象约束类似物。在动物模型中，9CUAB30已显示可防止ER阳性和ER阴性的乳腺癌，其效力与Targretin相似。另外，仅7天治疗后，观察到增殖和凋亡的调节。重要的是，基因表达阵列分析已被用来证明9CUAB30不是肝脏中的激动剂，这是组织选择性雷克尼素的所需标志。这项单臂IB研究旨在确定所选剂量下的9CUAB30是否会修饰乳腺组织生物标志物。因此，这项工作陈述概述了研究的要求，包括（但不限于）参与者应计，代理给药和患者随访以及相关的生物标志物分析。这项工作声明包括屏幕80参与者的协议活动，并在肿瘤状态分层的试验中注册40个，并在匹配的对照病例上执行生物标志物。