17-AAG IN PEDIATRIC PATIENTS WITH RECURRENT/REFRACTORY MALIGNANCIES

17-AAG 在患有复发性/难治性恶性肿瘤的儿科患者中的应用

• 批准号: 7605098
• 负责人: Lia Gore
• 金额: $ 0.04万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605098
• 关键词: 17-(Allylamino)-17-demethoxygeldanamycin; Childhood; Childhood Solid Neoplasm; Computer Retrieval of Information on Scientific Projects Database; Correlative Study; Diagnosis; Disease; Dose; Dose-Limiting; Eligibility Determination; Funding; Grant; HSP 90 inhibition; Inpatients; Institution; Malignant Neoplasms; Maximum Tolerated Dose; Numbers; Outpatients; Patients; Phase; Progressive Disease; Proteins; Recurrence; Refractory; Research; Research Personnel; Resources; Rest; Role; Solid Neoplasm; Source; Stable Disease; Standards of Weights and Measures; Toxic effect; United States National Institutes of Health; Week; adult leukemia; base; cancer cell; experience; leukemia; response; tumor

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 multicenter Phase I dose escalation trial of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG, NSC#330507) in patients with selected recurrent/refractory pediatric malignancies. The primary objectives of this study are to establish the Dose Limiting Toxicity (DLT) and the Maximum Tolerated Dose (MTD) of 17-AAG in patients with selected malignancies, and to determine the extent to which 17-AAG, administered at the MTD, alters the levels of key proteins known to influence proliferation and survival in cancer cells collected from patients with specific pediatric solid tumors and leukemias. Patients in this study must have disease that has progressed despite standard therapy or for which no effective standard therapy is known. Patients will be stratified by diagnosis at study entry to either a solid tumor or a leukemia stratum. Doses will be escalated, and the DLT and MTD will be determined independently for the two strata. The strata will be expanded at the MTD to allow for the conduct of more intensive biologic correlative studies. These studies are critical to help determine the role of HSP90 inhibition in these selected tumor types. Patients will be treated with 17-AAG primarily in the outpatient setting, although treatment as an inpatient is allowed as long as eligibility criteria are met. 17-AAG will be administered intravenously twice weekly for 2 weeks followed by a week's rest for patients with solid tumors. Based on the experience in adult leukemia patients, the rest week will be omitted in patients with leukemia; these patients will be treated twice weekly for 3 consecutive weeks. Patients may continue to receive treatment at a given dose level if no DLTs are observed and if the patient does not have progressive disease. There will be no limitation on the number of cycles that may be administered to a patient who has stable disease or evidence of an objective response to this agent.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这是一项关于17-N-烯丙氨基-17-去甲氧基格尔达那霉素(17-AAG，NSC#330507)的多中心I期剂量递增试验，用于部分复发/难治性儿童恶性肿瘤患者。这项研究的主要目的是确定17-AAG在特定恶性肿瘤患者中的剂量限制毒性(DLT)和最大耐受剂量(MTD)，并确定在MTD处给予17-AAG对从特定的儿科实体肿瘤和白血病患者收集的癌细胞中已知影响增殖和存活的关键蛋白质水平的影响程度。这项研究中的患者必须患有尽管标准治疗仍有进展的疾病，或者没有有效的标准治疗方法。患者将根据研究进入实体肿瘤或白血病层的诊断进行分层。剂量将逐步增加，两层的DLT和MTD将独立确定。 MTD的地层将扩大，以便进行更密集的生物相关研究。这些研究对于确定HSP90抑制在这些选定的肿瘤类型中的作用至关重要。患者将主要在门诊环境中接受17-AAG治疗，但只要符合资格标准，就允许作为住院患者进行治疗。17-AAG将每周两次静脉注射，持续两周，实体肿瘤患者随后休息一周。根据成人白血病患者的经验，白血病患者将省略休息一周；这些患者将每周治疗两次，连续3周。如果没有观察到DLT，如果患者没有进行性疾病，患者可以继续接受给定剂量水平的治疗。对于病情稳定或有证据表明对该制剂有客观反应的患者，可以给予的周期数将没有限制。