Panobinostat and Everolimus in Treating Patients With Metastatic or Unresectable Renal Cell Cancer That Does Not Respond to Treatment With Sunitinib Malate or Sorafenib Tosylate

Inclusion Criteria:

Patients must have histologically confirmed metastatic or unresectable renal cell carcinoma
Predominant clear cell component is required
Patients must have metastatic disease which has progressed on or within 6 months of stopping treatment with VEGFR receptor tyrosine kinase inhibitors
Previous therapy with bevacizumab, interleukin 2, or interferon alpha is also permitted
Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
Serum albumin >= 3g/dL
AST/SGOT and ALT/SGPT =< 2.5 x upper limit of normal (ULN)
Serum bilirubin =< 1.5 x ULN
Serum creatinine =< 1.5 x ULN or 24-hour creatinine clearance >= 50 ml/min
Serum potassium >= LLN
Serum phosphorous >= LLN
Serum total calcium (corrected for serum albumin) or serum ionized calcium >= LLN
Serum magnesium >= LLN
TSH and free T4 within normal limits (WNL); patients may be on thyroid hormone replacement
ANC >= 1.5 x 10^9/L
Platelets >= 100 x 10^9/L
Hb > 9 g/dL
INR < 1.3 (or < 3 on anticoagulants)
Fasting serum cholesterol =< 300 mg/dL OR =< 7.75 mmol/L AND fasting triglycerides =< 2.5 x ULN (in case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication
Baseline MUGA or ECHO must demonstrate LVEF >= the lower limit of the institutional normal
ECOG Performance Status of =< 2

Exclusion Criteria:

Pure papillary and chromophobe renal cell carcinoma, collecting duct tumors and transitional cell carcinoma are not eligible
Prior treatment with a pan-HDAC or mTOR inhibitor
Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.)
Patients who have had a major surgery of significant traumatic injury within 4 weeks of start of study drug and who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
Prior treatment with any investigational drug within the preceding 4 weeks
Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent; topical or inhaled corticosteroids are allowed
Patients should not receive immunization with attenuated live vaccines within one weeks of study entry or during study period; close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus (Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY2a typhoid vaccines)
Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin
Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
1) Symptomatic congestive heart failure of New York Heart Association Class III or 4
2) Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
3) Concomitant use of drugs with a risk of causing torsades de pointes
4) Severely impaired lung functions as defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air
5) Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN; optimal glycemic control should be achieved before starting trial therapy
6) Active (acute or chronic) or uncontrolled severe infections
7) Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis; a detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients; HBV DNA and HCV RNA PCR testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection
A known HIV seropositivity
Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
Patients with an active, bleeding diathesis
Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods; adequate contraception must be used throughout the trial and for 8 weeks after the last dose of study drug by both sexes
Adults of reproductive potential who are not using effective birth control methods; if barrier contraceptive are being used, these must be continued throughout this trial by both sexes; hormonal contraceptives are not acceptable as a sole method of contraception
Women of childbearing potential must have a negative urine or serum pregnancy test within 14 days prior to administration of everolimus
Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus)
Patients with a known hypersensitivity to everolimus (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients
History of noncompliance to medical regimens
Male patient whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment
Patients unwilling to or unable to comply with the protocol
Patients currently receiving strong or moderate CYP3A4 inhibitors or inducers; patients should not begin study drugs until at least 72 hours after the last dose (or longer, as indicated) of the inhibitor or inducer