Low Dose Decitabine + Interferon Alfa-2b in Advanced Renal Cell Carcinoma

Inclusion Criteria: * Patients must have histologically confirmed clear cell renal carcinoma that is metastatic or unresectable. In the absence of metastatic disease, patients who are deemed unresectable or inoperable will have a documented surgical opinion confirming this. Surgical opinion will be rendered either by surgical consultation or after presentation at our interdisciplinary conference. Patients with locally recurrent RCC are eligible, if surgical resection of local recurrence is not feasible or is refused by patient. * Patients with locally advanced unresectable RCC should have measurable or evaluable metastatic disease to be eligible for the protocol. Patients with bilateral renal cancer are eligible as long as both cancers are of clear cell type and patients have metastatic or unresectable disease. * Patients may have received up to two prior anti-cancer therapies (including receptor tyrosine kinase inhibitors or cytokine therapy) but no prior chemotherapy for renal cell carcinoma. Patients should have received prior standard therapy, or otherwise deemed ineligible for such therapies. * Patients must have measurable or clinically evaluable disease as defined by RECIST criteria. * Patients must be \>/= 14 days beyond the last administration of anti-cancer therapy, and must have recovered from the toxicities of prior therapy. * Patients must be \>/= 18 years of age. * ECOG performance status \</= 2 (Karnofsky \>/= 60%). * Patients must have adequate organ and marrow function, measured within 14 days of study entry, as defined below: * All Patients: Absolute neutrophil count \>/= 1,500/microL; Platelets \>/= 100,000/microL; Creatinine (serum) \</= 2.0 mg/dL * Patients without liver metastases: Total bilirubin \</= 1.5 mg/dL; AST(SGOT)/ALT(SGPT) \</= 2.5 X Institutional Upper Limit of Normal (IULN) * Patients with liver metastases: Total bilirubin \</= 1.5 x IULN; AST(SGOT)/ALT(SGPT) \</= 5 x IULN * The effects of decitabine and interferon on the developing human fetus are unknown. For this reason and because chemotherapy agents are known to be teratogenic, women of child-bearing potential and men 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. * Female patients of childbearing potential should have a normal plasma beta human chorionic gonadotropin (betaHCG). * Patients must give written informed consent prior to initiation of therapy in keeping with the policies of the institution. Patients with a history of major psychiatric illness must be judged able to fully understand the investigational nature of this study and the risks associated with the therapy. Exclusion Criteria: * Patients with active autoimmune disorders or who are receiving immunosuppressive therapy (including steroids or methotrexate) for any indication. * Patients may not receive any other investigational agents within two weeks of study entry. Patients may not receive any other investigational agents while on study. * Patients who have had major surgery within 2 weeks prior to entering the study, or have otherwise not adequately recovered from prior surgery. * Patients who have had palliative radiation therapy within 1 week prior to entering the study. * Patients with untreated or symptomatic brain metastases. * Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or potentially life-threatening cardiac arrhythmia. * Psychiatric illness or social situations which in the opinion of the investigator could interfere with the completion of the proposed treatment. * Pregnant women are excluded from this study because decitabine is an antimetabolite with the potential for teratogenic or abortifacient effects and interferon alfa-2b has abortifacient activity in animal studies. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with decitabine, breastfeeding should be discontinued if the mother is treated with decitabine or decitabine and interferon. * Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, patients known to be HIV-positive and receiving anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with the study agents.