Low Dose Decitabine + Interferon Alfa-2b in Advanced Renal Cell Carcinoma
Condition: Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Decitabine; Interferon Alfa-2b
Intervention description: 15 mg/m^2 IV Daily over one hour for 5 days; 0.5 million Units Subcutaneously Twice Daily Continuously. Interferon Alfa-2b will be added on cycle three, day one.
Intervention MeSH terms: Interferons; Interferon-alpha; Interferon alpha-2; Decitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Renal Cell Carcinoma; Renal Cell Cancer; Clear Cell; Kidney; Decitabine; Dacogen; 5-Aza-Deoxycytidine; Interferon Alfa-2b; Intron A®; RCC

Summary:

      Primary Objective:

        -  To determine the progression-free survival (PFS) times for patients with advanced renal
           cell carcinoma (RCC) treated with decitabine and interferon alfa-2b.

      Secondary Objectives:

        -  To determine the toxicity of the combination of decitabine and interferon alfa-2b at the
           proposed dose and schedule in patients with advanced RCC

        -  To determine overall response by Response Evaluation Criteria in Solid Tumors (RECIST)
           criteria for patients with advanced RCC treated with decitabine and interferon alfa-2b.

        -  To determine the overall survival times for patients with advanced RCC treated with
           decitabine and interferon.

        -  To study the effects of decitabine and interferon alfa-2b on DNA methylation and gene
           expression in patients' tumor and non-tumor tissues and their correlation with clinical
           outcomes.

        -  To characterize the modulation of cellular immunity induced by the combination of
           decitabine and interferon alfa-2b in patients with advanced RCC and to correlate these
           results with clinical outcomes.
    

Eligibility criteria:

        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.