Azacitidine in Treating Patients With Previously Treated Advanced Non-Small Cell Lung Cancer

Inclusion Criteria:

* Advanced (stage 4 or recurrent) NSCLC, not eligible for any curative intent treatment

  * Tumor must be histologically or cytologically confirmed
* Measurable disease (as defined by RECIST criteria)
* Patients may have up to two (and at least one) prior cytotoxic regimens in the metastatic setting

  * Prior adjuvant chemotherapy following resection or definitive chemo-radiation for patients with locally advanced disease is not included in this
  * Allowable systemic therapy in the metastatic setting includes 2 cytotoxic regimens and erlotinib and/or other non-cytotoxic drugs (i.e., erlotinib, sorafenib, and other tyrosine kinase inhibitors do not count as a "cytotoxic regimen")
  * Prior adjuvant therapy or definitive chemo-radiation is allowed if completed \> six months before the onset of "first-line" therapy in the metastatic setting - in this setting, adjuvant or definitive chemo-radiation will not "count" as one of the two cytotoxic regimens; if however, the patient relapses within six months from completion of adjuvant or definitive chemoradiation, then this therapy will be considered the first-line cytotoxic therapy
  * In the unusual circumstance where patients receive "adjuvant" therapy following resection of oligo-metastatic disease (for example brain metastasis and lung primary resections) and the treating physician decides to administer chemotherapy following all surgery, this will be considered "adjuvant" therapy and the same rules as noted above will apply for initiation of first-line systemic therapy
* No patients with uncontrolled brain metastases or leptomeningeal disease

  * Patients with controlled brain metastases are allowed
* ECOG performance status 0-2
* Absolute neutrophil count ≥ 1.5 x 10\^9/L
* Platelets ≥ 100,000 x 10\^9/L
* Hemoglobin ≥ 9.0 gm/100 mL
* Total bilirubin ≤ 1.5 mg/dL
* AST and ALT ≤ 2.5 x ULN
* Creatinine ≤ 1.5 mg/dL OR calculated creatinine clearance \> 50 mL/min
* No patients who are pregnant
* Women of childbearing potential must have a negative pregnancy test
* The patient must be willing to use adequate contraception for the duration of study treatment and up to four weeks following the last dose of drug
* Archival diagnostic material sufficient for microRNA evaluation/assessment is preferred, though optional

  * The presence of archival material will not preclude the need for pre and post treatment biopsies
* Willing to undergo biopsy pre-treatment and following first cycle

  * Biopsy may be from any accessible site (primary or metastatic)
* No known HIV or hepatitis B or C (though testing for this is not required)
* No uncontrolled intercurrent illness including, but not limited to:

  * Symptomatic CHF
  * Unstable angina pectoris
  * Serious cardiac arrhythmia
  * Serious infection
  * Psychiatric illness or social situations that would limit compliance with study requirements
* No patients who have significant psychiatric illness that, in the opinion of the principal investigator, would prevent adequate informed consent or render therapy unsafe
* Patients may not have had a prior invasive malignancy except for adequately treated non-melanoma cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 2 years

  * For example, a stage 1 (T1c) prostate cancer 2 years prior to a diagnosis of NSCLC would not be exclusionary, however, a metastatic prostate cancer currently receiving hormonal or chemotherapy would be excluded
* No other concurrent palliative radiotherapy
* Recovered from prior surgery, radiation, or chemotherapy to ≤ grade 2 toxicity
* Palliative radiation or surgical procedures (for example, endobronchial therapy) is allowed, but must have been completed \> 2 weeks prior to starting treatment
* No other investigational or commercial agents or therapies may be administered with the intent to treat the patient's malignancy
* No other concurrent investigational therapy