Phase I Clinical Trials of Novel Agents

描述(由申请人提供)：在过去的5年里，MSKCC的研究人员进行了涉及各种信号转导药物以及不寻常机制的新型药物的临床试验。该中心在进行与小分子、单抗和疫苗相关的第一阶段研究方面拥有丰富的经验。这项研究建议通过进行新的抗癌药物和药物调节方案的第一阶段研究来开发与癌症治疗相关的新信息，试图提高新药的治疗效果。在临床研究的同时，研究将评估研究药物的分布和代谢，并在临床生化和分子水平上检查它们的生物学效应。具体目标将是使用以下类别的药物进行第一阶段临床试验：1)基因表达的表观遗传调节调节剂(假定的分化治疗)，如维甲酸、组蛋白去乙酰酶抑制剂和去甲基化药物；2)信号转导靶标，如蛋白激酶C、AKT、HER2和细胞周期依赖激酶；3)肿瘤(组织特异性)治疗的第一阶段测试，如适用于前列腺癌等单一肿瘤类型的药物；以及4)免疫治疗。计划中的临床试验将由CTEP工作人员根据意向书授予。我们希望利用MSKCC的实验室和临床研究人员提供的实验室见解，为I期临床试验提供新的假设。相关科学包括药代动力学、基因表达、蛋白质表达、功能成像和活检材料中终点的评估，预计将是即将完成的研究的主要部分。

DESCRIPTION (provided by applicant): In the past 5 year, the MSKCC investigators have performed clinical trials involving a variety of signal transduction agents as well as novel agents of unusual mechanism. The center has extensive experience in the conduct of Phase I studies related to small molecules, monoclonal antibodies and vaccines. This research proposes to develop new information relevant to the treatment of cancer by conducting Phase I studies of new anticancer drugs and pharmacologic modulatory regimens which attempt to enhance the therapeutic efficacy of new drugs. Concurrent with the clinical studies, the research will evaluate the distribution and metabolism of the study drugs and examine their biological effects at the clinical biochemical and molecular level. The Specific Aims will be to perform Phase I clinical trials with agents from the following classes: 1) Modulators of epigenetic regulation of gene expression (putative differentiation therapy) such as retinoids, histone deacetylase inhibitors and demethylating agents; 2) Signal Transduction Targets such as protein kinase C, AKT, HER2 and cell cycle dependent kinases; 3) Phase I Testing of Tumor (Histology Specific) Therapies such as agents appropriate for a single tumor type like prostate cancer; and 4) Immunologic Therapy. The planned clinical trials are to be awarded by the CTEP staff in response to LOI's. We hope to take advantage of the laboratory insights provided by laboratory and clinical investigators at the MSKCC to provide new hypotheses for Phase I clinical testing. Correlative sciences including pharmacokinetics, gene expression, protein expression, functional imaging and assessment of endpoints in biopsy material are expected to be a major part of the studies to be done.