Azacitidine and Entinostat in Treating Patients With Metastatic Colorectal Cancer

OBJECTIVES:

Primary objectives

- To determine the preliminary efficacy of the combination of azacitidine and entinostat
in patients with metastatic colorectal cancer.

Secondary objectives

- To explore the effects of this regimen on the time to progression in these patients.

- To assess the toxicity of this regimen in these patients.

- To evaluate changes in promoter methylation of selected genes from DNA in circulating
serum samples.

- To determine changes in histone deacetylase activity and acetylation of H3 and H4
histones in pre- and post-treatment tumor biopsies.

- To evaluate correlations between these molecular effects and clinical outcomes
(response and time to progression).

OUTLINE: This is a multicenter study.

Patients receive azacitidine subcutaneously on days 1-5 and 8-10 and oral entinostat on days
3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable
toxicity.

Blood and tumor tissue samples are collected at baseline and periodically during courses 1-3
for DNA methylation, histone deacetylation activity, and acetylation of H3 and H4 histones
analysis by PCR, western blot, and RT-PCR assays.

After completion of study therapy, patients are followed up every 3-6 months for up to 3
years.