Capecitabine and Vorinostat in Treating Patients With Recurrent and/or Metastatic Head and Neck Cancer

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