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