azacitidine and entinostat in treating patients with stage i non-small cell lung cancer that has been removed by surgery

Conditions: Stage IA Non-Small Cell Lung Carcinoma; Stage IB Non-Small Cell Lung Carcinoma

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).

primary objectives: i. to assess the effect of 5-azacitidine and entinostat on the hazard of 3 year progression-free survival in patients with resected stage i non-small cell lung cancer. secondary objectives: i. to assess the safety, tolerability and toxicity of entinostat and 5-azacitidine in patients with resected stage i non-small cell lung cancer. ii. to explore the effect of entinostat and 5-azacitidine on median disease-free and overall survival in patients with resected stage i non-small cell lung cancer. iii. to assess the pharmacodynamic effects of 5-azacitidine and entinostat on dna methylation and gene re-expression in patients with resected stage i nsclc through analysis of sputum. iv. to estimate the effect of entinostat and 5-azacitidine on progression free survival comparing patients with n2 lymph nodes categorized as methylated pre-treatment with those who are categorized as unmethylated. v. to establish factors that predict clinical outcome in patients treated with combination epigenetic therapy by performing genome-wide analyses on pre-treatment tumor dna. outline: patients are randomized to 1 of 2 arms. arm i: patients receive azacitidine subcutaneously (sc) on days 1-5 and 8-10 and entinostat orally (po) once daily (qd) on days 3 and 10. treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. arm ii: patients receive standard of care. after completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

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