Vorinostat, Carboplatin, and Paclitaxel in Treating Patients With Advanced or Metastatic 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; paclitaxel; carboplatin; placebo; laboratory biomarker analysis
Intervention description: Given PO; Given IV; Given IV; Given PO; Correlative studies
Intervention MeSH terms: Paclitaxel; Carboplatin; Vorinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 94.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial is studying carboplatin, paclitaxel, and vorinostat to see how
      well they work compared with carboplatin, paclitaxel, and a placebo in treating patients with
      stage III or stage IV non-small cell lung cancer. Drugs used in chemotherapy, such as
      carboplatin and paclitaxel, 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 carboplatin and paclitaxel together with vorinostat is more effective than
      giving carboplatin and paclitaxel together with a placebo in treating non-small cell lung
      cancer
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed stage IIIB (with malignant pleural
             pericardial effusion) or stage IV non-small cell lung cancer

          -  No prior chemotherapy for advanced or metastatic disease

          -  ECOG performance status 0 or 1

          -  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

          -  Life expectancy of greater than 12 weeks

          -  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

          -  Vorinostat can cause fetal harm when administered to a pregnant woman; there are no
             adequate and well-controlled studies in pregnant women; if this drug is used during
             pregnancy, or if the patient becomes pregnant while taking this drug, the patient
             should be apprised of the potential hazard to the fetus

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier

          -  Patients may not be receiving any other investigational agents

          -  Patients with untreated brain metastases should be excluded from this clinical trial;
             however, patients who have stable brain disease (should be off corticosteroids) at
             least 3 weeks after completion of appropriate therapy are eligible

          -  Prior or current use of valproic acid, a HDAC inhibitor

          -  Peripheral neuropathy of severity greater than grade 1

          -  Known history of allergic reactions to paclitaxel

          -  Prior therapy with paclitaxel

          -  Inability to take oral medications on a continuous basis

          -  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

          -  Pregnant women are excluded from this study because vorinostat is an HDAC inhibitor
             with the potential for teratogenic or abortifacient effects; because there is an
             unknown but potential risk for adverse events in nursing infants secondary to
             treatment of the mother with vorinostat, breastfeeding should be discontinued if the
             mother is treated with vorinostat; these potential risks may also apply to other
             agents used in this study

          -  HIV-positive patients receiving combination antiretroviral therapy are ineligible
             because of the potential for pharmacokinetic interactions with vorinostat; 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 antiretroviral therapy when indicated