17-AAG IN PEDIATRIC PATIENTS WITH RECURRENT/REFRACTORY MALIGNANCIES

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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 recurrent/refractory pediatric 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 undergo stratification 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 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 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.