Capecitabine and Vorinostat in Treating Patients With Recurrent and/or Metastatic Head and Neck Cancer
Condition: Paranasal Sinus Squamous Cell Carcinoma; Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Oral Cavity Squamous Cell Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Hypopharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Hypopharyngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Oral Cavity Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Recurrence
Intervention: Capecitabine; Vorinostat
Intervention description: Given PO; Given PO
Intervention MeSH terms: Capecitabine; Vorinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 19 Years
Healthy volunteers: No

Summary:

      This partially randomized phase II trial studies giving capecitabine and vorinostat in
      treating patients with head and neck cancer that has come back after previous treatment or
      that has spread to other areas in the body. Drugs used in chemotherapy, such as capecitabine,
      work in different ways to stop the growth of tumor cells, either by killing the cells or by
      stopping them from dividing. Vorinostat may stop the growth of tumor cells by blocking some
      of the enzymes needed for cell growth. It is not yet known whether giving capecitabine
      together with vorinostat is more effective than capecitabine alone in treating patients with
      cancer of the head and neck cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed SCCHN or NPC that is
             recurrent and/or metastatic and that is not amendable to curative therapy by surgery
             or radiation; SCCHN originating from the following sites are eligible: oral cavity,
             oropharynx, larynx, hypopharynx and paranasal sinus are eligible; for patients with a
             diagnosis of SCCHN of unknown origin, their eligibility must be reviewed and approved
             by the principal investigator

          -  For patients with SCCHN, they may have received one prior targeted therapy for
             recurrent or metastatic disease (excluding histone deacetylase [HDAC] inhibitors)
             provided treatment is completed > 4 weeks prior to enrollment; they may have received
             prior systemic chemotherapy (ie, induction, concurrent or adjuvant) for SCCHN as part
             of the initial multimodality treatment for locally advanced disease if the
             chemotherapy is completed > 6 months prior to enrollment; patients are not eligible if
             they received fluorouracil (5-FU) or capecitabine previously as part of the initial
             multimodality treatment

          -  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 enrollment; patients are eligible if
             they received 5-FU as part of the initial multimodality treatment; patients are not
             eligible if they received capecitabine previously

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as >
             20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT)
             scan; indicator lesions must not have been previously treated with surgery, radiation
             therapy or radiofrequency ablation unless there is documented progression after
             therapy

          -  Patients must have completed any previous surgery or radiotherapy >= 4 weeks prior to
             enrollment

          -  Previously treated patients must have evidence of progressive disease, either
             clinically or radiographically, as assessed by the investigator

          -  Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Karnofsky > 60%)

          -  Life expectancy of greater than 12 weeks

          -  Absolute neutrophil count >= 1.5 x 10^9/L

          -  Platelets >= 100 x 10^9/L

          -  Total bilirubin =< 1.25 times upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 3 x ULN or =< 5 x ULN with documented liver metastases

          -  Creatinine =< 1.25 x ULN OR creatinine clearance >= 50 mL/min/1.73 m^2 for patients
             with creatinine levels above 1.25 x ULN

          -  12-lead electrocardiogram (ECG) with normal tracing, or non-clinically significant
             changes that do not require medical intervention; corrected QT (QTc) interval < 470
             msec, and without history of Torsades de Pointes or other symptomatic QTc abnormality

          -  Eligibility of patients receiving any medications or substances known to affect or
             with the potential to affect the activity of vorinostat will be determined following
             review of their case by the principal investigator

          -  Women of childbearing potential and men must be surgically sterilized, practicing
             abstinence, or agree to use 2 birth control methods prior to study entry and for the
             duration of study participation; the 2 birth control methods can be either be 2
             barrier methods or a barrier method plus a hormonal method to prevent pregnancy; the
             following are considered adequate barrier methods of contraception: diaphragm or
             sponge, and condom; other methods of contraception such as copper intrauterine device
             or spermicide may be used; appropriate hormonal contraceptives will include any
             registered and marketed contraceptive agent that contains an estrogen and/or a
             progestational agent (including oral, subcutaneous, intrauterine, or intramuscular
             agents); should a woman become pregnant or suspect she is pregnant while participating
             in this study, she should inform her treating physician immediately

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Patients must be willing and able to comply with scheduled visits, treatment plan,
             laboratory tests and other study procedures

          -  Willingness to discontinue taking any medications that are generally accepted to have
             a risk causing Torsades de Pointes during the study

        Exclusion Criteria:

          -  Past or current malignancy other than SCCHN or NPC, except for:

               -  Cervical carcinoma Stage 1B or less

               -  Non-invasive basal cell and squamous cell skin carcinoma

               -  Malignant melanoma with a complete response of a duration of > 10 years

               -  Radically treated prostate cancer (prostatectomy or radiotherapy) with normal
                  prostate specific antigen (PSA), and not requiring ongoing anti-androgen hormonal
                  therapy

               -  Other cancer diagnosis with a complete response of duration of > 5 years

          -  Patients may not be receiving any other investigational agents

          -  Patients with known brain metastases should be excluded from this clinical trial

          -  Prior use of capecitabine is not allowed

          -  Prior and concomitant treatment with HDAC inhibitors (such as valproic acid) are not
             allowed

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to vorinostat or other agents used in study

          -  Patients who are unable to take oral medications and / or who have a clinical or
             radiological diagnosis of bowel obstruction are ineligible

          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active
             infection, active peptic ulcer disease, myocardial infarction within 6 months prior to
             entry, congestive heart failure, symptomatic congestive heart failure, active
             cardiomyopathy, unstable angina pectoris, cardiac arrhythmia, uncontrolled
             hypertension or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if
             the mother is treated with vorinostat

          -  Human immunodeficiency virus (HIV)-positive patients are ineligible

          -  Patients with known dihydropyrimidine dehydrogenase (DPD) deficiency are excluded