Phase I Study of CUDC-101 With Cisplatin and Radiation in Subjects With Head & Neck Cancer

Inclusion Criteria: * Subjects with locally advanced, pathologically confirmed diagnosis of squamous cell carcinoma of the head and neck at the following sites: oral cavity, oropharynx, hypopharynx and larynx with either: * Stage IV p16 positive tumors and \>10 pack-years smoking history. * Stage III/IV p16 negative tumors, regardless of smoking history. * At least evaluable disease; one measurable site of disease according to RECIST (Version 1.1) criteria (at least 10 mm for conventional CT/MRI or spiral CT scan) is desirable. * Subjects enrolled in the MTD expansion cohort must have at least 1 tumor lesion that is suitable for repeat biopsy (pre- and post-CUDC-101 infusion). * Age ≥ 18 years * ECOG performance \< 2 * Life expectancy ≥ 3 months * If female, neither pregnant nor lactating * If of child bearing potential, must use adequate birth control throughout the participation in the treatment phase and for 60 days following the last study treatment. * Absolute neutrophil count ≥ 1,800/µL; platelets ≥ 100,000/µL; hemoglobin ≥ 8.0 g/dL, creatinine ≤ 1.5x upper limit of normal (ULN); total bilirubin ≤ 1.5x ULN; AST/ALT ≤ 2 x ULN. * Serum magnesium and potassium within normal limits (may be supplemented to achieve normal values) * Able to render informed consent and to follow protocol requirements. Exclusion Criteria: * Prior radiotherapy to the region of the study cancer or adjacent anatomical sites, or \> 25% of marrow-bearing area. * Prior chemotherapy for the current indication. * Prior therapy that specifically and directly targets EGFR, HER2 or HDAC. * Use of investigational agent(s) within 30 days prior to study treatment. * Primary tumor site of nasopharynx, sinuses, or salivary gland. * History of cardiac disease with a New York Heart Association (NYHA) Class II or greater congestive heart failure (CHF), myocardial infarction (MI) or unstable angina in the past 6 months prior to Day 1 of treatment, serious arrhythmias requiring medication for treatment. * Patients with prolonged QTc Interval \>450 msec. * Acquired Immune Deficiency Syndrome (AIDS) or known infection with human immunodeficiency virus (HIV). Testing is not required. * Known history of gastrointestinal bleeding, ulceration, or perforation within 6 months prior to study treatment. * Known history of stroke or cerebrovascular accident within 6 months prior to study treatment. * Symptomatic cardiac conduction abnormality within 12 months prior to study treatment. * Prior history of hearing impairment. * Known history of renal disease or ongoing renal impairment. * Any uncontrolled condition (such as active systemic infection, diabetes, hypertension), which in the opinion of the investigator, could affect the subjects participation in the study. * Prior allergic reaction to cisplatin, carboplatin or other platinum-containing compounds. * Central nervous system metastases.