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Pilot Phase II Study of 5-Azacytidine in Previously Treated Patients With Advanced NSCLC

Phase 2
18 Years
Open (Enrolling)
Recurrent Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

Thank you

Trial Information

Pilot Phase II Study of 5-Azacytidine in Previously Treated Patients With Advanced NSCLC


I. To determine the ability of 5-azacytidine to cause DNA hypomethylation and re-expression
of silenced tumor suppressor genes when stratified for high or low expression of mir29a, b,
and c.


I. To compare the molecular studies (mir29 expression and tumor suppressor gene methylation)
between archival tissue, fresh biopsy pre-treatment samples, and post-treatment fresh

II. To determine the overall response rate by CT (RECIST 1.1 criteria) and PET (EORTC PET
response criteria), PFS, and OS of patients treated with azacytidine in the second- or
third-line setting.

III. To correlate the blood microRNA profiles (and changes in microRNA profiles) with
response to azacytidine.


Patients receive azacitidine subcutaneously on days 1-7. Courses repeat every 28 days in the
absence of disease progression or unacceptable toxicity.

Patients undergo tissue and blood sample collection at baseline and periodically during
study treatment for correlative studies. After completion of study treatment, patients are
followed up for 12 weeks.

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

- 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

- No patients who have significant psychiatric illness that, in the opinion of the
principal investigator, would prevent adequate informed consent or render therapy

- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

DNA hypomethylation and re-expression of silenced tumor suppressor genes when stratified for low or high expression of mir29

Outcome Description:

The change in mean methylation of the genes between the patients with a low mir29 and a high mir29 expression will be evaluated by a two-sample t-test. Secondary analyses include a multivariate regression where all 5 changes in methylation will be regressed on mir29 expression (low vs. high) and adjusted for patient demographic and clinical attributes at baseline.

Outcome Time Frame:

Up to 12 weeks after completion of study treatment

Safety Issue:


Principal Investigator

Gregory Otterson

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

January 2011

Completion Date:

Related Keywords:

  • Recurrent Non-Small Cell Lung Cancer
  • Stage IV Non-Small Cell Lung Cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center Columbus, Ohio  43210-1240