A Phase II Study of Vorinostat and Capecitabine in Recurrent and/or Metastatic Squamous Cell Carcinoma of Head and Neck (SCCHN) and Nasopharyngeal Carcinoma (NPC)

Inclusion Criteria:

- Histologically or cytologically confirmed disease meeting 1 of the following
criteria:

- Squamous cell carcinoma of the head and neck (SCCHN)

- Oral cavity

- Oropharynx

- Larynx

- Hypopharynx

- Paranasal sinus

- SCCHN of unknown origin must be reviewed and approved by principal
investigator

- Nasopharyngeal carcinoma (NPC)

- Patients with NPC must have completed one prior chemotherapy regimen for recurrent or
metastatic disease at least 4 weeks prior to enrollment; in addition, they may have
received prior systemic chemotherapy (ie, induction, concurrent or adjuvant) for NPC
as part of the initial multimodality treatment for locally advanced disease if the
chemotherapy is completed > 6 months prior to enrolment; patients are eligible if
they received 5-FU as part of the initial multimodality treatment; patients are not
eligible if they received capecitabine previously

- Measurable disease defined as ≥ 1 lesion that can be accurately measured in ≥ 1
dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or
as ≥ 10 mm by spiral CT scan

- Indicator lesions must not have been previously treated with surgery,
radiotherapy, or radio frequency ablation unless there is documented progression
after therapy

- No known brain metastases

- ECOG performance status (PS) 0-2 (Karnofsky PS 60-100%)

- Life expectancy > 12 weeks

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Total bilirubin ≤ 1.25 times upper limit of normal (ULN)

- AST and ALT ≤ 3 times ULN (≤ 5 times ULN for patients with documented liver
metastases)

- Creatinine ≤ 1.25 times ULN OR creatinine clearance ≥ 50 mL/min

- ECG with normal tracing or non-clinically significant changes that do not require
medical intervention

- QTc interval < 470 msec and without history of Torsade de Pointes or other
symptomatic QTc abnormality

- Not pregnant or nursing

- Fertile patients must use effective contraception (abstinence or 2 birth control
methods) prior to and for the duration of study

- Willing and able to comply with schedule visits, treatment plan, laboratory tests,
and other study procedures

- More than 5 years since another malignancy except stage 0-IB cervical carcinoma,
non-invasive basal cell or squamous cell skin carcinoma, or radically treated
prostate cancer (prostatectomy or radiotherapy) with normal PSA and not requiring
ongoing anti-androgen hormonal therapy

- More than 10 years since malignant melanoma

- No inability to take oral medications and/or a clinical or radiological diagnosis of
bowel obstruction

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to vorinostat or other agents used in this study

- No uncontrolled intercurrent illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Active peptic ulcer disease

- Myocardial infarction within the past 6 months

- Congestive heart failure

- Symptomatic congestive heart failure

- Active cardiomyopathy

- Unstable angina pectoris

- Cardiac arrhythmia

- Uncontrolled hypertension

- Psychiatric illness and/or social situations that would limit compliance with
study requirements

- Not HIV positive

- No known dihydropyrimidine dehydrogenase (DPD) deficiency

- No concurrent radiotherapy (except for metastatic bone lesions)

- At least 4 weeks since prior targeted therapy for recurrent or metastatic squamous
cell carcinoma of the head and neck (SCCHN)

- No prior or other concurrent histone deacetylase (HDAC) inhibitors (e.g.,
valproic acid)

- More than 6 months since prior systemic chemotherapy (i.e., induction, concurrent,
or adjuvant) as part of the initial multimodality treatment for locally advanced
disease

- No prior fluorouracil as part of initial modality treatment for patients with
SCCHN

- Prior fluorouracil for patients with nasopharyngeal carcinoma (NPC) allowed

- No prior capecitabine for patients with SCCHN or NPC

- At least 4 weeks since prior surgery or radiotherapy

- Concurrent medication or substances known to affect or with the potential to affect
the activity of vorinostat will be reviewed in a case by case by principal
investigators

- No other concurrent investigational agents

- No concurrent medications that are generally accepted to have risk of causing
Torsades de Pointes

- No other concurrent anticancer therapy

- Palliative interventions, such as paracentesis or palliative surgery, allowed