9 CIS-RETINOIC ACID AND INTERFERON-A IN KAPOSIS SARCOMA

描述：(申请人的描述)这项工作的总体目标 建议评估9-顺式维甲酸(9-CRA)联合应用的疗效 干扰素-a治疗HIV相关性卡波西病的新方法 肉瘤(KS)。我们将通过连续进行两个步骤来实现这一目标 学习。第一项研究将是I期临床试验，以确定 联合用药的最大耐受量(MTD)。后续研究将 是利用先前确定的MTD进行的II期临床试验 检测联合治疗的抗肿瘤反应。生物参数 将被测量的将包括KS肿瘤组织上的维甲酸受体亚型， 9-CRA药代动力学，以及艾滋病毒复制指标，如p24 抗原和HIV核糖核酸。这项建议是基于临床前和临床 经验表明干扰素-a和维甲酸以及 临床前证据表明，9-CRA具有更广泛的受体结合和 与其他维甲酸相比，更有利的药代动力学。这个 就这一提议进行合作的调查人员已经有很长一段时间了 在对艾滋病毒KS患者进行临床试验方面的跟踪记录。在……里面 此外，我们有充足的病人资源以及强大的支持 结构，以确保成功完成拟议的研究。

DESCRIPTION: (Applicant's Description) The overall objective of this proposal is to evaluate the efficacy of 9-cis retinoic acid (9-cRA) combined with interferon-a (INF-a) as novel treatment for HIV associated Kaposi's sarcoma (KS). We will achieve this objective by conducting two sequential studies. The first study will be a Phase I clinical trial to determine the maximally tolerated dose (MTD) of the combination. The follow up study will be a Phase II clinical trial utilizing the previously determined MTD to measure the antitumor response of combination therapy. Biologic parameters to be measured will include retinoid receptor subtypes on KS tumor tissue, 9-cRA pharmacokinetics, as well as indicators of HIV replication such as p24 antigen and HIV RNA. This proposal is based on preclinical and clinical experience suggesting synergy between INF-a and retinoids as well as preclinical evidence showing that 9-cRA has broader receptor binding and more favorable pharmacokinetics as compared to other retinoids. The investigators collaborating on this proposal have a long and established track record in the conduct of clinical trials in patients with HIV KS. In addition, we have ample patient resources as well as a strong support structure to ensure the successful completion of the proposed research.