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

• Maximum-tolerated dose of vorinostat in combination with paclitaxel and carboplatin [ Designated as safety issue: Yes ]
• Safety and tolerability of vorinostat in combination with paclitaxel and carboplatin [ Designated as safety issue: Yes ]

• Response rate in patients with lung, head and neck, and esophageal cancers assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
• Effects of therapy on HIV viral load and CD4 cell count [ Time Frame: Baseline and 6, 12, and 18 weeks ] [ Designated as safety issue: No ]

• Response rate in patients with lung, head and neck, and esophageal cancers [ Designated as safety issue: No ]
• Effects of therapy on HIV viral load and CD4 cell count [ Designated as safety issue: No ]

This phase I clinical trial is studying the side effects and the best dose of vorinostat when given together with paclitaxel and carboplatin in treating patients with metastatic or recurrent solid tumors and HIV infection. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving vorinostat together with paclitaxel and carboplatin may kill more tumor cells.

PRIMARY OBJECTIVES:

I. Determine the safety and tolerability of vorinostat in combination with paclitaxel and carboplatin in patients with solid tumors and HIV infection.

II. Determine the maximum-tolerated dose (MTD) of this combination in this patient population.

SECONDARY OBJECTIVES:

I. Preliminarily assess response rates to this therapeutic combination in patients with lung, head and neck, and esophageal cancers.

II. Evaluate the pathological characteristics of non-AIDS-defining cancers of the upper aerodigestive tract.

III. Determine the presence and oncogenic activity of human papillomavirus (HPV) infection in tumor tissue and to correlate HPV infection with clinical outcomes.

IV. Investigate the effects of vorinostat with chemotherapy on patient immune status, HIV viral load, and latent viral reservoirs in memory T cells using highly sensitive assays.

V. Investigate possible pharmacokinetic interactions between paclitaxel and antiretroviral therapy in persons with HIV infection.

VI. Investigate possible pharmacokinetic interactions between ritonavir and vorinostat in patients with HIV infection.

OUTLINE: This is a multicenter, dose-escalation study of vorinostat followed by an expansion cohort study. Patients are stratified according to highly active antiretroviral therapy (HAART) (ritonavir-based HAART vs other or no HAART vs efavirenz-based HAART [expansion cohort]).

Patients receive oral vorinostat once daily on days 1-5 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 3. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Some patients undergo blood sample collection at baseline and periodically during course 1 for pharmacokinetic studies and HIV viral load analysis.

After completion of study therapy, patients are followed up every 6 months for up to 3 years.

• HIV Infection
• Recurrent Anal Cancer
• Recurrent Breast Cancer
• Recurrent Esophageal Cancer
• Recurrent Gastric Cancer
• Recurrent Metastatic Squamous Neck Cancer With Occult Primary
• Recurrent Non-small Cell Lung Cancer
• Recurrent Ovarian Epithelial Cancer
• Recurrent Salivary Gland Cancer
• Recurrent Squamous Cell Carcinoma of the Hypopharynx
• Recurrent Squamous Cell Carcinoma of the Larynx
• Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
• Recurrent Squamous Cell Carcinoma of the Nasopharynx
• Recurrent Squamous Cell Carcinoma of the Oropharynx
• Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
• Recurrent Verrucous Carcinoma of the Larynx
• Recurrent Verrucous Carcinoma of the Oral Cavity
• Salivary Gland Squamous Cell Carcinoma
• Stage IV Anal Cancer
• Stage IV Breast Cancer
• Stage IV Esophageal Cancer
• Stage IV Gastric Cancer
• Stage IV Non-small Cell Lung Cancer
• Stage IV Ovarian Epithelial Cancer
• Stage IV Salivary Gland Cancer
• Stage IV Squamous Cell Carcinoma of the Hypopharynx
• Stage IV Squamous Cell Carcinoma of the Larynx
• Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity
• Stage IV Squamous Cell Carcinoma of the Nasopharynx
• Stage IV Squamous Cell Carcinoma of the Oropharynx
• Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
• Stage IV Verrucous Carcinoma of the Larynx
• Stage IV Verrucous Carcinoma of the Oral Cavity
• Unspecified Adult Solid Tumor, Protocol Specific

• Drug: vorinostat
  Given orally
  Other Names:

  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
• Other: diagnostic laboratory biomarker analysis
  Correlative studies
• Other: pharmacological study
  Correlative studies
  Other Name: pharmacological studies
• Drug: carboplatin
  Given IV
  Other Names:

  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
• Drug: paclitaxel
  Given IV
  Other Names:

  • Anzatax
  • Asotax
  • TAX
  • Taxol

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