A MULTICENTER PHASE I TRIAL OF 17-N-ALLYLAMINO-17-DEMETHOXY GELDANAMYCIN

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这是一项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期试验，用于复发/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在复发/难治性儿童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17-AAG在多大程度上改变从儿童实体肿瘤和白血病患者收集的癌细胞中已知的影响癌细胞增殖和存活的关键蛋白质水平。患者必须患有尽管标准治疗仍有进展的疾病，或者没有已知有效的标准治疗的疾病。患者将在研究开始时根据诊断进行分层，要么是实体肿瘤，要么是白血病。岩层将单独进行评价。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。实体瘤患者每周静脉给药两次，持续两周，然后休息一周。根据成人白血病患者的经验，白血病患者将省略休息一周。这些患者将连续3周每周接受两次治疗。

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 Trial of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG, NSC#330507) in patients with 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 recurrent/refractory pediatric malignancies and to determine the extent to which the 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 pediatric solid tumors and leukemias. Patients must have disease that has progressed despite standard therapy or for which no effective standard therapy is known. Patients will undergo stratification by diagnosis at study entry to either a solid tumor or a leukemia stratum. Strata will be evaluated separately. Patients will be treated with 17-AAG primarily in the outpatient setting, although treatment as an inpatient will be permitted as long as eligibility criteria are met. Drug will be administered intravenously twice per week for 2 weeks followed by a 1 week rest for patients with solid tumors. Based on experience in adult leukemia patients, the rest week will be omitted in patients with leukemia. These patients will be treated twice per week for 3 consecutive weeks.