Phase I Clinical Trials of Novel Agents

描述（由申请人提供）：在过去的5年中，MSKCC研究人员进行了涉及多种信号转导药物以及异常机制的新型药物的临床试验。该中心在开展与小分子、单克隆抗体和疫苗相关的I期研究方面拥有丰富的经验。本研究拟通过开展新的抗癌药物和药理调节方案的I期研究，试图提高新药的治疗效果，以开发与癌症治疗相关的新信息。在临床研究的同时，本研究将对研究药物的分布和代谢进行评价，并在临床生化和分子水平上检验其生物学效应。具体目标将是使用以下类别的药物进行I期临床试验：1)基因表达表观遗传调控调节剂（假定的分化治疗），如类维生素a、组蛋白去乙酰化酶抑制剂和去甲基化剂；2)信号转导靶点，如蛋白激酶C、AKT、HER2和细胞周期依赖性激酶；3)肿瘤（组织学特异性）治疗的I期试验，如适合前列腺癌等单一肿瘤类型的药物；4)免疫治疗。计划的临床试验将由CTEP的员工根据意向书授予。我们希望利用MSKCC实验室和临床研究人员提供的实验室见解，为I期临床测试提供新的假设。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终点评估在内的相关科学预计将成为研究的主要部分。

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.