AT13387 in Adults With Refractory Solid Tumors

Background: \- The experimental drug AT13387 has been shown to have some anticancer effects against tumor cells by blocking a protein that affects other proteins inside certain cancer cells, and helps to prevent the cancer cells from reproducing and spreading. AT13387 has not been tested in humans, and researchers are interested in investigating whether it can be used to treat solid tumors that have not responded to standard treatments. Objectives: \- To investigate the safety and effectiveness of AT13387 in individuals with solid tumors. Eligibility: \- Individuals at least 18 years of age who have solid tumors that have not responded to standard treatments. Design: * Participants will be screened with a physical examination and medical history, as well as blood tests and tumor imaging studies. * AT13387 will be given in 28-day cycles of treatment. Participants will receive AT13387 twice a week (2 days in a row) for the first 3 weeks of the cycle, followed by a fourth week without the drug. * Participants will have regular blood and urine samples, imaging studies, eye examinations, and tumor biopsies to monitor the effects of the treatment. * Participants will continue treatment with AT13387 unless serious side effects develop or the tumor stops responding to treatment.

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.