Clinical trial NCT01384799 (phase 1, status: completed)
Conditions: head and neck cancer
ICD codes: C76.0, C47.0, C49.0, C77.0, D17.0, D21.0, D36.11
Drugs: cudc-101, cisplatin
SMILES: COC1=C(OCCCCCCC(=O)NO)C=C2C(NC3=CC=CC(=C3)C#C)=NC=NC2=C1, [H][C@@]12N(C)C3=CC(OC)=C(C=C3[C@@]11CCN3CC=C[C@](CC)([C@@]13[H])[C@@]([H])(OC(C)=O)[C@]2(O)C(=O)OC)[C@]1(C[C@@]2([H])CN(CC(CC)=C2)CC2=C1NC1=CC=CC=C21)C(=O)OC
Eligibility criteria:

        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.