High Dose IL 2 and Entinostat in RCC

Inclusion Criteria

• •Age ≥ 18 years at the time of consent.
• •ECOG Performance Status of 0 within 14 days prior to registration.
• •Life expectancy of greater than 6 months.
• •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.
• •Patients must have measurable or evaluable disease by RECIST 1.1.
• •Up to two prior therapies for RCC are allowed. One prior therapy must contain an immune checkpoint inhibitor.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
• •White blood cell (WBC) ≥ 3,000 K/mm3
• •Absolute Neutrophil Count (ANC) ≥ 1,500/mm3
• •Leukocytes ≥ 3,000/mm3
• •Platelets ≥ 100,000/mm3
• •Hemoglobin (Hgb) ≥ 12 g/dL
• •Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
• •Calculated creatinine clearance ≥ 50 mL/min
• •Corrected calcium ≤ 10 mg/dL
• •Urine protein \< 1 +; if ≥ 1+, a 24 hour urine protein should be obtained and be \< 1,000 mg
• •Total Bilirubin ≤ 1.5 × upper limit of normal (ULN)
• •Aspartate aminotransferase (AST) ≤ 2.5 × ULN
• •Alanine aminotransferase (ALT) ≤ 2.5 × ULN
• •Lactate Dehydrogenase Within Normal Limits
• •International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN
• •Females of childbearing potential must have a negative serum pregnancy test during screening and within 3 days prior to receiving first dose of study medication. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
• •Females of childbearing potential and males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 90days after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method.
• •Pulmonary: FEV1 \> 2.0 liters or \> 75% of predicted for height and age
• •Cardiac: 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. NOTE: 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.
• •CNS: No history of cerebrovascular accident, transient ischemic attacks, central nervous system or brain metastases. NOTE: Patients with CNS metastases should have a head CT/MRI within 21 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 no evidence of recurrent disease for 6 months are eligible.
• •Known active hepatitis B (e.g., hepatitis B surface antigen-reactive) or hepatitis C (e.g., hepatitis C virus ribonucleic acid \[qualitative\]). Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody \[HBc Ab\] and absence of HBsAg) are eligible. NOTE: HBV DNA test must be performed prior to study treatment. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• •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%.