Azacitidine and Entinostat Before Chemotherapy in Treating Patients With Advanced Non-small Cell Lung Cancer
Condition: Recurrent Non-Small Cell Lung Carcinoma; Stage IIIA 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: Azacitidine; Azacitidine; Docetaxel; Entinostat; Gemcitabine Hydrochloride; Irinotecan Hydrochloride; Laboratory Biomarker Analysis; Pemetrexed Disodium
Intervention description: Given SC; Given PO; Given IV; Given PO; Given IV; Given IV; Correlative studies; Given IV
Intervention MeSH terms: Gemcitabine; Azacitidine; Docetaxel; Irinotecan; Pemetrexed; Camptothecin; Entinostat; Histone Deacetylase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well azacitidine and entinostat before
      chemotherapy works in treating patients with non-small cell lung cancer that has spread to
      other places in the body. Drugs used in chemotherapy, such as azacitidine, irinotecan
      hydrochloride, gemcitabine hydrochloride, docetaxel, and pemetrexed disodium, work in
      different ways to stop the growth of tumor cells, either by killing the cells, by stopping
      them from dividing, or by stopping them from spreading. Entinostat may stop the growth of
      tumor cells by blocking some of the enzymes needed for cell growth. Giving azacitidine and
      entinostat before chemotherapy may work better in treating patients with non-small cell lung
      cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically proven non-small cell lung cancer;
             tumor tissue must be available from all patients prior to initiation of protocol
             therapy, either from original diagnostic biopsy, or biopsy performed prior to
             initiation of protocol therapy

          -  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 for
             non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional
             techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic
             resonance imaging (MRI), or calipers by clinical exam

          -  Patients must have received 1 prior platinum containing doublet regardless of mutation
             status

          -  Patients with targetable mutation i.e. epidermal growth factor receptor (EGFR) or
             anaplastic lymphoma kinase (ALK), must have been treated with at least 1 prior
             tyrosine kinase inhibitor (TKI)

          -  Prior immunotherapy is allowed

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky >= 70%)

          -  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

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transferase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transferase [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

          -  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 she or her partner is participating in this study, she should inform
             her treating physician immediately

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 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 who are receiving any other investigational agents

          -  Patients with uncontrolled brain metastases; patients with brain metastases must have
             stable neurologic status following local therapy (surgery or radiation) for at least 4
             weeks, and must be without neurologic dysfunction that would confound the evaluation
             of neurologic and other adverse events; patients may be treated with steroids as
             clinically indicated

          -  Patients with liver metastases that replace greater than 30% of the liver parenchyma

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to entinostat, azacitidine, mannitol, irinotecan, docetaxel, pemetrexed,
             or gemcitabine, or other agents used in the study

          -  Uncontrolled inter-current illness including, but not limited to, ongoing or active
             infection, New York Heart Association (NYHA) class 3-4 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; breastfeeding should be discontinued if
             the mother is treated on this protocol

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible