AT13387 in Adults With Refractory Solid Tumors

Background: * AT13387 is a synthetic Hsp90 inhibitor that has demonstrated improved characteristics over other Hsp90 inhibitors. AT13387 has a long tumor retention half-life and prolonged inhibitory effect on its known oncogenic client proteins. * AT13387 has demonstrated activity against multiple cancer cell lines and tumor xenografts in pre-clinical models. Primary Objectives: * Define the safety and tolerability of AT13387 administered on a QDx2 every week, 3 weeks out of 4 scheduled, in adults with refractory solid tumors. * Establish the maximum tolerated dose (MTD) of AT13387 administered on a QDx2 every week, 3 weeks out of 4 schedule, in adults with refractory solid tumors. Secondary Objectives: * Determine the pharmacokinetics (PK) of AT13387 administered on a QDx2 every week, 3 weeks out of 4 schedule, in adults with refractory solid tumors. * Assess pharmacodynamic (PD) markers of Hsp90 inhibition and modulation of Hsp90 client proteins by AT13387 in tumor tissue, serum, and PBMCs. Eligibility: -Study participants must have histologically confirmed solid tumor malignancy that has progressed or recurred after at least one line of chemotherapy, or for which no standard treatment option exists. Participants enrolling in the expansion phase must have disease amenable to biopsy with willingness to undergo pre- and post-treatment biopsies (Remove the HER 2 archival tissue). Study Design: * This study will follow an accelerated titration design 2B with initial dose levels increased in 100% increments. * The accelerated phase ends when one patient experiences a dose-limiting toxicity or two patients experience Grade 2 drug-related toxicity during the first cycle; when dose level 3 is reached; or at first instance of Grade 2 ocular toxicity in any cycle. * AT13387 will be administered intravenously, over 1 hour, on 2 consecutive days, 3 out of 4 weeks, every 28 days (i.e., on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle). * PK and PD studies will be conducted in cycle 1 only. Once the MTD is established, 10 additional patients, will be entered at the MTD to further define toxicity and perform PD studies at this dose; pre- and post-treatment tumor biopsies will be mandatory for these patients. * CT scans will be performed at baseline and every 2 cycles for restaging. * Up to 37 patients may be treated. * Study participants will be offered optional participation in an ongoing NCI imaging study at baseline with a repeat scan following the last dose of AT13387 in cycle 1.