Azacitidine and Entinostat in Treating Patients With Stage I Non-Small Cell Lung Cancer That Has Been Removed By Surgery
Condition: Stage IA Non-Small Cell Lung Carcinoma; Stage IB Non-Small Cell Lung Carcinoma
MeSH terms: Carcinoma; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms
Intervention: Azacitidine; Entinostat; Laboratory Biomarker Analysis
Intervention description: Given SC; Given PO; Correlative studies
Intervention MeSH terms: Azacitidine; Entinostat; Histone Deacetylase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study combines the deoxyribonucleic acid (DNA) methyltransferase inhibitor,
      5-azacitidine (5-AZA), with an orally bioavailable histone deacetylase inhibitor, entinostat
      (SNDX-275), for the adjuvant treatment of patients with resected stage I non-small cell lung
      cancer (NCSLC).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must be status post complete (R0) surgical resection of pathologically-proven
             NSCLC (stage IA-IB according to AJCC version 7)

          -  Patients must be at least 4 weeks out from completion of surgery

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  Absolute neutrophil count >= 1,000/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin =< 1.5 X institutional upper limit of normal

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
             =< 2.5 X institutional upper limit of normal

          -  Creatinine =< 1.5 X institutional upper limit of normal

          -  The effects of entinostat and 5-azacitidine on the developing human fetus at the
             recommended therapeutic dose are unknown; for this reason, 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

        Exclusion Criteria:

          -  Patients must be within 8 weeks of completing surgery

          -  Patients who have received prior chemotherapy or radiation for treatment of their
             current diagnosis of lung cancer

          -  Patients with sub-lobar resections (ie: wedge resection or segmentectomy)

          -  Patients without mediastinal lymph node specimens from mediastinoscopy or surgery (at
             least level R4 or 7 for right sided tumors OR at least level 5, 6 or 7 for left sided
             tumors)

          -  Patients may not be receiving any other investigational agents

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to entinostat, 5-azacitidine or other agents used in the study

          -  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 entinostat and 5-azacitidine are
             agents 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 entinostat or 5-azacitidine, breastfeeding should be
             discontinued if the mother is treated on this protocol; these potential risks may also
             apply to other agents used in this study

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible because of the potential for pharmacokinetic interactions with
             entinostat or 5-azacitidine; in addition, these patients are at increased risk of
             lethal infections when treated with marrow-suppressive therapy