Inclusion Criteria:

- Patients must have pathological diagnosis of renal cell carcinoma that is metastatic
or surgically unresectable; the histology must be clear cell carcinoma or predominant
clear cell carcinoma

- No prior systemic therapies for RCC are allowed; prior palliative radiation to
metastatic lesion(s) is permitted, provided there is at least one measurable and/or
evaluable lesion(s) that has not been irradiated

- Patients must have measurable or evaluable disease

- Eastern Cooperative Oncology Group (ECOG) performance status 0

- Life expectancy of greater than 6 months

- Hemoglobin >= 12 g/dL

- Leukocytes >= 3,000/mm^3

- Absolute neutrophil count >= 1,500/mm^3

- Platelets >= 100,000/mm^3

- Total bilirubin =< 1.5 x laboratory upper limit of normal

- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
=< 2.5 x laboratory upper limit of normal

- Creatinine =< 1.5 x laboratory upper limit of normal or Calculated Creatinine
clearance of >= 50 ml/min

- Lactate dehydrogenase (LDH) within normal limits (WNL)

- Corrected calcium =< 10 mg/dL

- Prothrombin time (PT)/international normalized ratio (INR) =< 1.5

- Urine protein < 1+; if >= 1+, 24 hour urine protein should be obtained and should be
< 1000 mg

- Forced expiratory volume (FEV) 1 >= 2.0 liters or >= 75% of predicted for height and
age; (pulmonary function tests [PFTs] are required for patients over 50 or with
significant pulmonary or smoking history)

- No evidence of congestive heart failure, symptoms of coronary artery disease,
myocardial infarction less than 6 months prior to entry, serious cardiac arrhythmias,
or unstable angina; patients who are over 40 or have had previous myocardial
infarction greater than 6 months prior to entry will be required to have a negative
or low probability cardiac stress test for cardiac ischemia

- No history of cerebrovascular accident or transient ischemic attacks

- The effects of entinostat on the developing human fetus at the recommended
therapeutic dose are unknown; for this reason women of child-bearing potential must
agree to use adequate contraception (hormonal or barrier method of birth control;
abstinence) prior to study entry and for the duration of study participation; should
a woman become pregnant or suspect she is pregnant while participating in this study,
she should inform her treating physician immediately; men with female partners of
child bearing potential must also agree to use adequate contraception

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients who have received prior systemic therapy for metastatic RCC are not eligible

- Concurrent use of valproic acid is not allowed

- Patients may not be receiving any other investigational agents

- Patients with central nervous system (CNS) metastases; patients should have a head
CT/MRI within 28 days prior to treatment initiation; any imaging abnormality
indicative of CNS metastases will exclude the patient from the study; patients with
previously excised/gamma knifed solitary or oligometastases and controlled disease
are eligible

- Any medical condition that would preclude adequate evaluation of the safety and
toxicity of the study combination

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure (New York Association Class II, III,
or IV), angina pectoris requiring nitrate therapy, recent myocardial infarction (<
the last 6 months), cardiac arrhythmia, history of cerebrovascular accident (CVA)
within 6 months, hypertension (defined as blood pressure of > 160 mmHg systolic
and/or > 90 mmHg diastolic on medication) history of peripheral vascular disease, or
psychiatric illness/social situations that would limit compliance with study
requirements

- Pregnant women are excluded from this study because entinostat is a histone
deacetylase (HDAC) inhibitor agent with the potential for teratogenic or
abortifacient effects; because there is an unknown but potential risk for adverse
events in nursing infants secondary to treatment of the mother with entinostat,
breastfeeding should be discontinued if the mother is treated with entinostat

- Human immunodeficiency virus (HIV)-positive patients receiving combination
antiretroviral therapy are ineligible because of the potential for pharmacokinetic
interactions with entinostat; in addition, these patients are at increased risk of
lethal infections when treated with marrow-suppressive therapy; appropriate studies
will be undertaken in patients receiving combination anti-retroviral therapy when
indicated

- Serious or non-healing wound, ulcer or bone fracture

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to day 1 therapy

- Anticipation of need for major surgical procedures during the course of the study

- Left ventricular ejection function < 45%