Belinostat (PXD101) to Treat Tumors of the Thymus at an Advanced Stage

Background: Cisplatin-containing chemotherapy is the standard of care for advanced unresectable thymoma and thymic carcinoma. New options for treatment are necessary in patients with advanced thymoma and thymic carcinoma that have progressed on cisplatin-containing therapy. Histone deacetylase inhibitors have shown promising clinical activity in many malignancies. Belinostat, a potent histone deacetylase inhibitor, is a promising agent, which may have activity in patients with thymic malignancies. Objectives: * To assess objective response rate according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria for belinostat monotherapy. * To assess safety of belinostat. * To evaluate time to response, duration of response, progression-free survival and overall survival. * To identify chromosomal gains or losses and gene methylation status by comparative genomic hybridization and methylation microarrays in thymoma / thymic carcinomas in relation to clinical outcome. * To assess expression levels of particular proteins on the pretreatment tumor sample, by immunohistochemistry (IHC) and correlate them with clinical outcome. * To identify and measure changes in p21 and protein hyperacetylation in peripheral blood mononuclear cells (PBMC), and vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in plasma and correlate them with clinical outcome. * To measure changes in modulation of T-cell function in peripheral blood lymphocytes. Eligibility: * Patients with histologically confirmed thymic carcinoma or thymoma who have previously been treated on at least one platinum containing chemotherapy regimen. * Measurable disease by RECIST criteria. * Adequate renal, hepatic and hematopoietic function. * QT Interval must be less than 500 msec at baseline by electrocardiogram (EKG) (Fridericia's formula used for correction). * No major surgery, radiotherapy, or chemotherapy within 28 days of belinostat therapy. Design: * Patients will receive belinostat as a 30-minute intravenous (IV) infusion of 1000 mg/m\^2/day during days 1-5 every 3 weeks. After 12 cycles of treatment, cycles will be given every 4 weeks. * Treatment with belinostat alone will continue until disease progression. * Toxicity will be assessed every cycle by the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 until December 31, 2010, and by CTCAE Version 4.0 beginning January 1, 2011. * Tumor response assessments by RECIST criteria will be performed every 2 cycles. After 12 cycles, response assessment will be every 3 cycles. * Correlative studies including comparative genomic hybridization, methylation microarray analysis, and tissue immunohistochemistry studies will be done on existing tumor blocks. * Blood samples for circulating plasma biomarkers of response including VEGF will be drawn the first day of cycle 1 and 2 as well as cycle 1, day 3. * Blood samples for protein hyperacetylation and T cell modulation analyses will be drawn the first day of cycle 1 and 2.