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,
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
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.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
DNA hypomethylation and re-expression of silenced tumor suppressor genes when stratified for low or high expression of mir29
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.
Up to 12 weeks after completion of study treatment
Ohio State University Comprehensive Cancer Center
United States: Food and Drug Administration
|Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center||Columbus, Ohio 43210-1240|