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

描述：（申请人的描述）本申请的总体目标是： 建议评估9-顺式维甲酸（9-cRA）联合 干扰素-α（INF-α）作为HIV相关卡波西病的新疗法 肉瘤（KS）。 我们将通过两个连续的 问题研究 第一项研究将是一项I期临床试验，以确定 最大耐受剂量（MTD）。 后续研究将 是一项II期临床试验，使用先前确定的MTD， 测量联合治疗的抗肿瘤反应。 生物学参数 待测量的将包括KS肿瘤组织上的类视色素受体亚型， 9-cRA药代动力学，以及HIV复制的指标，如p24 抗原和HIV RNA。 该提案基于临床前和临床 经验表明INF-α和类维生素A之间的协同作用以及 临床前证据显示9-cRA具有更广泛的受体结合， 与其他类维生素A相比，药代动力学更有利。 的 调查人员合作这项建议有一个长期和既定的 在HIV KS患者中进行临床试验的跟踪记录。 在 此外，我们有充足的病人资源以及强大的支持， 以确保研究的顺利完成。

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.