Suberoylanilide Hydroxamic Acid in Treating Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer
Condition: Recurrent Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: vorinostat; laboratory biomarker analysis
Intervention description: Given PO; Correlative studies
Intervention MeSH terms: Vorinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 19 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well suberoylanilide hydroxamic acid works in treating
      patients with stage IIIB, stage IV, or recurrent non-small cell lung cancer. Drugs used in
      chemotherapy, such as suberoylanilide hydroxamic acid, work in different ways to stop the
      growth of tumor cells, either by killing the cells or by stopping them from dividing.
      Suberoylanilide hydroxamic acid may also stop the growth of tumor cells by blocking some of
      the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed non-small cell lung
             carcinoma, Stage IV (distant metastases), stage IIIB with malignant pleural effusion,
             or recurrent disease

          -  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 CT scan

          -  Prior therapy: no more than 1 prior cytotoxic chemotherapy regimen for their Stage
             IIIB/IV or recurrent disease; no previous irradiation to the only area of measurable
             disease, unless that site had subsequent progression of disease; radiation therapy
             must be completed at least 3 weeks prior to initiating study drug

          -  Stage IV patients with brain metastases are eligible providing the brain metastases
             are clinically and radiologically stable 4 weeks after treatment with surgery and/or
             radiation therapy, and they are not taking steroids

          -  Life expectancy greater than 3 months

          -  ECOG performance status 0 or 1 (Karnofsky >= 70%)

          -  Patients must have normal organ and marrow function as defined below:

          -  Leukocytes >= 3,000/mcL

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin within normal institutional limits

          -  AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal

          -  Creatinine within normal institutional limits OR creatinine clearance >= 60
             mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

          -  Peripheral neuropathy =< grade 1

          -  Caution needs to be exercised when using SAHA with medications or substances known to
             affect or with the potential to affect the activity or pharmacokinetics of SAHA; since
             grapefruit juice is known to interact with the CYP450 enzymes, it is recommended that
             patients abstain from consuming grapefruit, grapefruit juice, and other grapefruit
             containing products during this study

          -  The effects of SAHA on the developing human fetus at the recommended therapeutic dose
             are unknown; for this reason and because HDAC inhibitors are known to be teratogenic,
             women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation; 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 should not have taken valproic acid, another histone deacetylase inhibitor,
             for at least 2 weeks prior to enrollment

        Exclusion Criteria:

          -  Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or
             mitomycin C) or radiotherapy within 3 weeks prior to entering the study

          -  Patients may not be receiving any other investigational agents

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to SAHA

          -  Any other active malignancy in the past 5 years except non-melanoma skin cancers

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Because there is an unknown but potential risk for adverse events in nursing infants
             secondary to treatment of the mother with SAHA, breastfeeding should be discontinued
             if the mother is treated with SAHA

          -  HIV-positive patients receiving combination antiretroviral therapy are ineligible
             because of the potential for pharmacokinetic interactions with SAHA; in addition,
             these patients are at increased risk of lethal infections when treated with
             marrow-suppressive therapy; appropriate studies will be undertaken in patients
             receiving combination anti-retroviral therapy when indicated