Azacitidine and MS-275 in Treating Patients With Recurrent Advanced Non-Small Cell Lung Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC):

  • Metastatic or unresectable disease
• Patient must have failed at least one previous chemotherapy regimen
• 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) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan
• Life expectancy > 12 weeks
• Leukocytes >= 3,000/mcL
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2 (Karnofsky >= 60%)
• Absolute neutrophil count >= 1,500/mcL
• Platelet count >= 100,000/mcL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT] and alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73m^2 for patients with creatinine levels above institutional normal
• The effects of entinostat and 5-AZA 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
• Patients who have a major objective response to treatment on this protocol, and who experience progression of disease at least 1 year after completion of protocol consent and therapy, may be re- retreated at the previously effective dose and schedule

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 may not be 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 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, 5-AZA, mannitol 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-AZA 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-AZA, 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-AZA; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy