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.