Phase I Clinical Trials of Novel Agents

新药I期临床试验

• 批准号: 6581626
• 负责人: DAVID R SPRIGGS
• 金额: $ 38.4万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-16 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6581626
• 关键词: all trans retinol; antineoplastics; biological signal transduction; bryostatin; cell differentiation; ceramides; cis platinum compound; clinical research; clinical trial phase I; combination cancer therapy; cooperative study; cytotoxicity; dosage; drug resistance; drug screening /evaluation; human subject; human therapy evaluation; mitomycin C; monoclonal antibody; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy; neoplasm /cancer pharmacology; neoplasm /cancer vaccine; nuclear magnetic resonance spectroscopy; paclitaxel; patient oriented research; pharmacokinetics; polymerase chain reaction; protein kinase C; all trans retinol; antineoplastics; biological signal transduction; bryostatin; cell differentiation; ceramides; cis platinum compound; clinical research; clinical trial phase I; combination cancer therapy; cooperative study; cytotoxicity; dosage; drug resistance; drug screening /evaluation; human subject; human therapy evaluation; mitomycin C; monoclonal antibody; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy; neoplasm /cancer pharmacology; neoplasm /cancer vaccine; nuclear magnetic resonance spectroscopy; paclitaxel; patient oriented research; pharmacokinetics; polymerase chain reaction; protein kinase C

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.

描述（由申请人提供）：在过去的5年中，MSKCC研究人员进行了临床试验，涉及各种信号转导剂以及新型机制的新型药物。该中心在与小分子，单克隆抗体和疫苗有关的I期研究中具有丰富的经验。这项研究建议通过对新抗癌药物和药理学调节方案进行I期研究，以开发与癌症治疗相关的新信息，该研究试图增强新药的治疗功效。与临床研究同时，该研究将评估研究药物的分布和代谢，并检查其在临床生化和分子水平上的生物学作用。具体目的是对以下类别的药物进行I期临床试验：1）基因表达的表观遗传调节调节剂（假定分化治疗），例如类维生素类似，组蛋白脱乙酰基酶抑制剂和脱甲基化剂； 2）信号转导靶标，例如蛋白激酶C，AKT，HER2和细胞周期依赖性激酶； 3）I期肿瘤（组织学特异性）疗法的I期测试，例如适合于单一肿瘤类型的药物（如前列腺癌）； 4）免疫疗法。计划的临床试验将由CTEP人员授予LOI的授予。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，以提供I期临床测试的新假设。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，预计将是要完成的研究的主要部分。