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