Azacitidine and Entinostat in Treating Patients With Newly Diagnosed Stage IA-IIIA Non-Small Lung Cancer Undergoing Surgery
Azacitidine and Entinostat in Treating Patients With Newly Diagnosed Stage IA-IIIA Non-Small Lung Cancer Undergoing Surgery
This pilot clinical trials studies azacitidine and entinostat in treating patients with newly
 diagnosed stage IA-IIIIA non-small cell lung undergoing surgery. Drugs used in chemotherapy,
 such as azacitidine, work in different ways to stop the growth of tumor cells, either by
 killing the cells or by stopping them from dividing. Entinostat may stop the growth of cancer
 tumor cells by blocking some of the enzymes needed for cell growth. Giving azacitidine with
 entinostat may be an effective treatment for non-small cell lung cancer.
PRIMARY OBJECTIVES:

 I. To measure reversal of aberrant genome-wide promoter methylation and gene re-expression in
 paired, pre- and post- treatment lung tumor tissue pairs from patients with newly diagnosed,
 surgically resectable non-small cell lung cancer before and after exposure to a single
 neoadjuvant cycle of 5-azacytidine (azacitidine) and entinostat.

 SECONDARY OBJECTIVES:

 I. To measure the 3-year disease-free survival of operable non-small cell lung cancer (NSCLC)
 patients who receive 1 cycle of preoperative epigenetic treatment.

 II. To determine any potential toxicities, and reversibility of toxicities, of a single
 pre-operative cycle of 5-azacytidine and entinostat.

 OUTLINE:

 Patients receive azacitidine subcutaneously (SC) on days 1-6 and 8-10 and entinostat orally
 (PO) on days 3 and 10. Patients undergo surgery between days 11-20 (this period can be
 extended 10 more days if adverse events from therapy impose a surgical risk).

 After completion of study treatment, patients are followed up at 4 weeks, every 3 months for
 2 years and then every 6 months for 1 year.
Inclusion Criteria:

 -  Undergoing a diagnostic biopsy, including computed tomography (CT)-guided or
 bronchoscopic for suspected diagnosis of NSCLC

 -  Able to understand and sign an informed consent discussing the risks and benefits of
 obtaining a concurrent research biopsy; patients who have a fresh frozen biopsy
 available secondary to institutional tissue collection protocols may substitute such a
 biopsy for the study-required pre-treatment biopsy

 -  Histologically confirmed diagnosis of operable NSCLC that has not been previously
 treated

 -  Clinical stage IA-IIIA

 -  Appropriate candidate for surgical management, in the opinion of the treating thoracic
 surgeon

 -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 at the time of
 initiation of neoadjuvant epigenetic therapy

 -  Absolute neutrophil count > 1,000/mcL

 -  Platelets > 100,000/mcL

 -  Total bilirubin < 1.5 x institutional upper limit of normal (ULN)

 -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
 [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
 < 2.5 x institutional ULN

 -  Creatinine < 1.5 x institutional ULN

 -  Able to understand and sign an informed consent

 -  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

 -  Inclusion of women and minorities:

 -  Both men and women and members of all races and ethnic groups are eligible for
 this trial; the coordinating center will be responsible for ensuring each
 participating site is accruing a representative sample consistent with the
 estimate of population representation in the site's geographical location for
 race and ethnic groups as determined by the Census Bureau to assure overall
 target goals are met

 Exclusion Criteria:

 -  Patients who have received prior chemotherapy or radiation for their diagnosis of lung
 cancer

 -  Patients may not be receiving any other investigational agent

 -  History of allergic reactions attributed to compounds of similar chemical or biologic
 composition to entinostat or 5-azacytidine

 -  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; breastfeeding should be discontinued if
 the mother is treated on this protocol

 -  Any co-morbid condition that' in the view of the attending physician' renders the
 patient at high risk from treatment complications

 -  Human immunodeficiency virus (HIV) positive patients on combination antiretroviral
 therapy are ineligible

 -  Known or suspected hypersensitivity to azacitidine or mannitol

 -  Patients with advanced malignant hepatic tumors

 -  Use of anti-neoplastic or anti-tumor agents that are not part of the study therapy,
 including chemotherapy, radiation therapy, immunotherapy, and hormonal anticancer
 therapy, is not permitted while participating in this study; Note: study participants
 with stage II or III NSCLC, or stage I NSCLC with tumor size greater than 4 cm, should
 be offered standard adjuvant platinum-based chemotherapy in accordance with local
 practice (post-operatively)