Phase I Study of CUDC-101 With Cisplatin and Radiation in Subjects With Head & Neck Cancer
Phase I Study of CUDC-101 With Cisplatin and Radiation in Subjects With Head & Neck Cancer
This is a phase I dose escalation study of CUDC-101 in combination with concurrent cisplatin
 and radiation therapy in patients with locally advanced head and neck cancer. CUDC-101 is a
 multi-targeted agent designed to inhibit epidermal growth factor receptor (EGFR), human
 epidermal growth factor receptor Type 2 (Her2) and histone deacetylase (HDAC). The study is
 designed to establish the safety, tolerability and maximum tolerated dose (MTD) of CUDC-101
 when administered in combination with concurrent cisplatin and radiation over an 8-week
 treatment course, consisting of a one week run-in period of CUDC-101 administered alone,
 followed by seven weeks of combination treatment with CUDC-101, cisplatin and radiation
 therapy.
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.