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

靶向视黄酸受体（RAR）的类维生素A和靶向类维生素A X受体（RXR）的类rexinoids代表了两类具有有效预防乳腺癌能力的潜在药物，并已被广泛研究。9cUAB 30是一种新的RXR选择性维甲酸，它是9 cis UAB 30的构象受限类似物。在动物模型中，9cUAB30已被证明可以预防ER阳性和ER阴性乳腺癌，其效力与Targretin相似。此外，仅在处理7天后就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于证明9cUAB 30不是肝脏中的激动剂，这是组织选择性rexinoid的理想标志。 这项单臂IB期研究旨在确定选定剂量的9cUAB30是否改变乳腺组织生物标志物。 因此，本工作说明书概述了研究要求，包括（但不限于）受试者招募、药物给药和患者随访以及相关生物标志物分析。本工作说明书包括筛选80名受试者并招募40名受试者参加试验的方案活动，试验按肿瘤的ER状态分层，并对匹配的对照病例进行生物标志物检测。

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.