Vorinostat in Combination With Chemoradiation in Locally Advanced HPV Negative HNSCC

Inclusion Criteria: * Subjects must have histologically or cytologically confirmed stage III or IV HPV negative squamous cell carcinoma of the oral cavity, oropharynx or hypopharynx, tumors is deemed to be either unresectable or locally advanced. * Subjects must have received no prior therapies (chemotherapy or radiotherapy) for this disease * Age \>18 years. Because the low occurrence of HNSCC in the pediatric population, children are excluded from this study * ECOG Performance status ≤ 2 * Subjects must have normal organ and marrow function as defined below * Hemoglobin ≥ 9.0 g/dl (transfusion permitted) * Leukocytes ≥ 3,000/mcL * Absolute neutrophil count ≥ 1,500/mcL * Platelet count ≥ 100,000/mcL * Total bilirubin within normal institutional limits * AST (SGOT) ≤ 2.5 X institutional upper limit of normal * ALT (SGPT) ≤ 2.5 X institutional upper limit of normal * Serum Creatinine clearance (\> 50 ml/min) * Based on findings from animal studies and its mechanism of action, vorinostat can cause fetal harm when administered to a pregnant woman. There are insufficient data on vorinostat use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In animal reproduction studies, vorinostat crossed the placenta and caused adverse developmental outcomes at exposures approximately 0.5 times the human exposure based on AUC0-24 hours. For this reason, women of child-bearing potential and men must agree to use adequate contraception…