Azacitidine and Entinostat in Treating Patients With Metastatic Colorectal Cancer
Condition: Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer
MeSH terms: Rectal Neoplasms; Colonic Neoplasms; Recurrence
Intervention: entinostat; azacitidine; laboratory biomarker analysis
Intervention description: Given orally; Given SC; Correlative studies
Intervention MeSH terms: Azacitidine; Entinostat; Histone Deacetylase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving azacitidine together with entinostat works in
      treating patients with metastatic colorectal cancer. Drugs used in chemotherapy, such as
      azacitidine, work in different ways to stop the growth of tumor cells, either by killing the
      cells or by stopping them from dividing. Entinostat may stop the growth of tumor cells by
      blocking some of the enzymes needed for cell growth. Giving azacitidine together with
      entinostat may kill more tumor cells.
    

Eligibility criteria:

        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