Azacitidine and Entinostat in Treating Patients With Metastatic Colorectal Cancer

Inclusion Criteria:

Histologically confirmed metastatic colorectal cancer
Measurable disease
Patient has failed ≥ 2 prior chemotherapy regimens
Not a candidate for curative resection

No CNS metastases within ≤ 2 years

Treatment for brain metastasis and whole brain disease that has remained stable for > 3 months allowed
Patients who have not been treated with steroid therapy may be allowed
ECOG performance status 0-1
Life expectancy ≥ 12 weeks
Leukocytes ≥ 3,000/mm^3
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST and ALT ≤ 2.5 times ULN
Creatinine normal OR creatinine clearance ≥ 60 mL/min
Negative pregnancy test
Not pregnant or nursing
Fertile patients must use effective contraception
Sensory neuropathy ≤ grade 2 allowed
Willing to provide tissue and blood samples
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat, azacitidine, mannitol, or other agents used in the study

No uncontrolled intercurrent illness including, but not limited to, any of the following:

Ongoing or active infection
NYHA class II-IV symptomatic congestive heart failure
Unstable angina pectoris
Cardiac arrhythmia
Psychiatric illness and/or social situations that would limit compliance with study requirements
No history of severe bleeding without thrombocytopenia
No concurrent radiotherapy including palliative treatment
Toxicities from prior therapy have resolved to ≤ grade 1
More than 4 weeks since prior chemotherapy (> 6 weeks for nitrosoureas or mitomycin C)
More than 4 weeks since prior major surgical procedure
No prior histone deacetylase inhibitors (including valproic acid) or demethylating agents
No concurrent investigational agents
No concurrent combination antiretroviral therapy in HIV-positive patients
No concurrent investigational or commercial anticancer agents or therapies