Vorinostat in Combination With Paclitaxel and Carboplatin in Treating Patients With Metastatic or Recurrent Solid Tumors and HIV Infection

Inclusion Criteria:

• Histologically confirmed solid malignancy meeting 1 of the following criteria:

  • Non-small cell lung cancer
  • Head and neck squamous cell carcinoma
  • Non-gastroesophageal junction esophageal cancer

  • Solid tumor that is sensitive to carboplatin and/or taxanes including, but not limited to, any of the following (dose-escalation phase only):

    • Salivary gland cancer
    • Gastric cancer
    • Breast cancer
    • Ovarian cancer
    • Anal cancer
    • No Kaposi sarcoma
• Metastatic or unresectable disease and considered incurable
• Known HIV infection by ELISA, positive western blot, or any other federally approved (licensed) HIV test

• Measurable disease

  • At least 1 measurable tumor
• No known brain metastases
• Hormone receptor status not specified
• Menopausal status not specified
• ECOG performance status (PS) 0-2 (Karnofsky PS 50-100%)
• Life expectancy > 12 months
• WBC ≥ 3,000/mm³
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Total bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal
• Creatinine normal OR creatinine clearance ≥ 50 mL/min
• Serum magnesium normal
• Serum potassium normal
• CD4 count > 150/mm³ within the past 2 weeks
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use adequate contraception (hormonal or barrier method of birth control, or abstinence) prior to, during, and for ≥ 3 months after study completion
• Must be capable of complying with study protocol
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or other agents used in study (including hypersensitivity to paclitaxel, Cremophor, or platinum-based therapy)
• Able to take oral medication (vorinostat tablets must be swallowed whole)
• No peripheral neuropathy > grade 1

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

  • Ongoing or active infection
  • Opportunistic infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness and/or social situations that would limit compliance with study requirements
• Recovered to ≤ grade 1 toxicities
• No more than 1 prior systemic therapy for palliative treatment of metastatic or unresectable relapsed disease
• At least 4 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas or mitomycin C) given with curative intent
• Prior taxane, including paclitaxel or docetaxel, and/or platinum exposure allowed provided patients did not experience disease progression within 3 months after the platinum-based therapy

• Any prior or concurrent antiretroviral therapy allowed provided patient has been on a stable regimen for ≥ 4 weeks with no intention to change the regimen within 8 weeks after study entry

  • No concurrent zidovudine or stavudine

• No prior vorinostat or other known HDAC inhibitors as cancer therapy

  • At least 2 weeks since prior valproic acid
• No other concurrent investigational agents
• No concurrent ketoconazole