CLINICAL TRIAL: PI & PHARMACOKINETIC STUDY OF DRUG FOR SOLID TUMORS & LYMPHOMAS

临床试验：PI

• 批准号: 7951280
• 负责人: CHANDRA BELANI
• 金额: $ 0.09万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7951280
• 关键词: Animals; Apoptosis; Clinical Research; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Cutaneous; Data; Drug Kinetics; Drug usage; Enzymes; Excision; Functional disorder; Funding; Goals; Grant; Half-Life; Hepatic; Histones; Hour; In Vitro; Institution; Lymphoma; Lysine; Metabolism; Multicenter Trials; Pathway interactions; Patients; Pharmaceutical Preparations; Phase; Proteins; Recurrent disease; Research; Research Personnel; Resources; Solid Neoplasm; Source; Systemic Therapy; T-Cell Lymphoma; United States National Institutes of Health; Vorinostat; cell growth; inhibitor/antagonist; neoplastic cell; transcription factor; tumor growth; tumor progression

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a Phase 1, multicenter trial to determine the pharmacokinetic disposition of vorinostat is patients with varying degrees of hepatic dysfunction. Vorinostat is an inhibitor of Histone deacetylases (HDAC), enzymes that catalyze the removal of acetyl groups from the lysine residues of proteins, including histones and transcription factors. HDAC inhibitors can induce tumor cell growth arrest, differentiation, or apoptosis in vitro and inhibit tumor growth in animals and the eventual goal is to use this drug to treat solid tumors, and therefore tumor progression will be a secondary aim of the study. Vorinostat has recently been approved by the US FDA (400 mg PO QD) for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies. Vorinostat has a short half life of less than 2 hours. The major pathways of metabolism of vorinostat involve glucuronidation and There are no data regarding the appropriate use of vorinostat in patients with hepatic dysfunction.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此，可以在其他清晰的条目中表示。列出的机构是 对于中心，这不一定是调查员的机构。 这是一项第一阶段的多中心试验，用于确定伏诺替替纳斯塔特的药代动力学处置是具有不同程度的肝功能障碍的患者。 Vorinostat是组蛋白脱乙酰基酶（HDAC）的抑制剂，该酶是催化从蛋白质的赖氨酸残基中去除乙酰基的酶，包括组蛋白和转录因子。 HDAC抑制剂可以在体外诱导肿瘤细胞生长停滞，分化或凋亡，并抑制动物的肿瘤生长，最终的目标是使用该药物治疗实体瘤，因此肿瘤进展将是该研究的第二个目标。 Vorinostat最近已获得美国FDA（400 mg PO QD）的批准，用于治疗皮肤T细胞淋巴瘤（CTCL）患者的皮肤表现，这些患者在两种全身性疗法上患有渐进，持久性或经常性疾病。 Vorinostat的半衰期不到2小时。伏地代谢的主要途径涉及葡萄糖醛酸化，并且没有有关肝功能障碍患者适当使用伏地的数据。