Genome-Wide Methylation and Gene Re-Expression Analysis of Resectable Lung Tumor Tissue Pairs Obtained Pre- and Post-Treatment With 5-Azacytidine and Entinostat
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.
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.
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.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Change in aberrant genome-wide promoter methylation
Genome-wide DNA methylation and gene expression profiles of each pre- and post-treatment tumor will be assessed using validated DNA methylation and gene expression arrays. Response will be measured based on the degree of epigenomic reprogramming (i.e., number of genes affected, degree of demethylation, and class of genes [e.g., PRC2]) and pathways affected.
Baseline up to day 20
University of New Mexico
United States: Food and Drug Administration
|University of Texas Southwestern Medical Center||Dallas, Texas|
|University of Kentucky||Lexington, Kentucky 40536-0098|
|University of New Mexico||Albuquerque, New Mexico 87131|