Randomized Phase II Trial of Adjuvant Combined Epigenetic Therapy With 5-azacitidine and Entinostat in Resected Stage I Non-small Cell Lung Cancer Versus Standard Care

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

- ECOG performance status =< 2

- Absolute neutrophil count >= 1,000/mcL

- Platelets >= 100,000/mcL

- Total bilirubin =< 1.5 X institutional upper limit of normal

- AST(SGOT)/ALT(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

- 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